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Insulin Glulisine (Monograph)

Brand name: Apidra
Drug class: Rapid-acting Insulins
Chemical name: [3B-L-Lysine,29B-L-glutamic acid] insulin (human)
Molecular formula: C258H384N64O78S6
CAS number: 207748-29-6


Antidiabetic agent; rapid-acting human insulin analog prepared using recombinant DNA technology and special laboratory strain of nonpathogenic Escherichia coli (K12).

Uses for Insulin Glulisine

Diabetes Mellitus

Treatment of type 1 or type 2 diabetes mellitus in adults who require a rapid-acting insulin for control of hyperglycemia.

Used in conjunction with a longer-acting insulin (e.g., isophane [NPH] insulin human, insulin glargine), except when administered via an external controlled-infusion device (pump).

At least as effective for glycemic control as insulin human (regular) or insulin lispro.

May provide greater convenience compared with insulin human (regular) in timing of insulin injections in relation to meals; clinical relevance of this difference remains to be established.

Used by IV infusion in appropriately monitored patients; American Diabetes Association (ADA) states that insulin glulisine offers no advantage over regular crystalline insulin in patients who require IV insulin.

Insulin Glulisine Dosage and Administration


Administer by sub-Q injection, continuous sub-Q infusion, or IV infusion.

Sub-Q Injection

For solution and drug compatibility information, see Compatibility under Stability.

When used as a mealtime insulin to control postprandial hyperglycemia, administer within 15 minutes before a meal or 20 minutes after starting a meal.

Administer by sub-Q injection using a conventional insulin syringe or an insulin injection pen (e.g., OptiClik) using BD ultra-fine needles. Apidra 3-mL cartridges are intended for use with the OptiClik injection pen; use of other injection pens with the cartridge may lead to inaccurate dosing.

Consult accompanying labeling for proper assembly, administration, and care of the injection pen. If the OptiClik device malfunctions, may withdraw insulin glulisine from the cartridge system into a U-100 insulin syringe and inject.

Inject into abdominal wall, thigh, or upper arm. Follow a planned rotation of injection sites within an injection area.

Sub-Q Infusion

For solution and drug compatibility information, see Compatibility under Stability.

Administer by continuous sub-Q infusion into the abdominal wall using an external controlled-infusion device (e.g., Disetronic H-Tron plus V100; D-Tron; MiniMed models 506, 507, 507c, and 508).

Replace infusion set (reservoir, tubing, and catheter) at least every 48 hours; replace insulin glulisine in the reservoir and select new infusion site.

Consult manufacturer’s labeling for specialized administration techniques (e.g., length of infusion, frequency of changing infusion sets) or other details specific to insulin glulisine. Consult manual provided by manufacturer of sub-Q infusion device for additional information on general use of the pump.

IV Administration

For solution and drug compatibility information, see Compatibility under Stability.

Administer by IV infusion in a setting that allows appropriate clinical and laboratory monitoring. (See Hypoglycemia and Hypokalemia under Cautions.)


For IV infusion, dilute in 0.9% sodium chloride injection to a concentration of 1 unit/mL.


Dosage of insulin glulisine is expressed in terms of USP units.

Insulin glulisine and insulin human are equipotent on a unit-for-unit basis with regard to glucose-lowering activity. (See Pharmacokinetics.)

More rapid onset and shorter duration of action than insulin human (regular). May require a longer-acting insulin or insulin infusion therapy to maintain adequate glycemic control.

Individualize dosage based on blood glucose determinations to obtain optimum therapeutic effect. No specific dosage recommendations by the manufacturer.

Whenever possible, patients should self-monitor blood glucose concentrations.

Glucose monitoring is particularly important for patients receiving insulin via an external infusion pump.

Make any dosage change cautiously and only under medical supervision. Changes in insulin therapy (e.g., strength, timing of dosing, manufacturer, type, method of administration, or species [animal insulins no longer commercially available in US]) may necessitate adjustments in dosage of insulin glulisine or concomitant antidiabetic agents.

Insulin dosage adjustment may be necessary if patient changes usual physical activity or meal plan, or during times of illness, emotional disturbances, or stress.


Diabetes Mellitus
Type 1
Sub-Q Injection

Usually, initial total insulin dosages range from 0.2–1 units/kg daily.

As part of a meal-related regimen, basal insulin requirements (e.g., using insulin detemir, insulin glargine) usually comprise 40–60% of the total daily insulin dosage, with the remainder given preprandially as rapid- or short-acting insulin.

Sub-Q Infusion

When used in external infusion pumps, a portion of the total dosage is given as meal-related injections, with the remainder as a basal infusion. Individualize dosage; adjust dosage regularly based on blood glucose determinations.

Type 2
Sub-Q Injection

In patients not controlled on intermediate-acting or long-acting insulin, some clinicians suggest initiating preprandial therapy with a rapid-acting insulin (e.g., insulin glulisine), with the preprandial injection comprising 40–50% of the total insulin dosage and the remainder (50–60%) given as a basal insulin.

Sub-Q Infusion

When used in external infusion pumps, a portion of the total dosage is given as meal-related injections, with the remainder as a basal infusion. Individualize dosage; adjust dosage regularly based on blood glucose determinations.

Special Populations

Hepatic Impairment

Dosage reduction may be required; carefully monitor blood glucose concentrations and adjust dosage as necessary. (See Elimination: Special Populations, under Pharmacokinetics.)

Renal Impairment

Dosage reduction may be required; carefully monitor blood glucose concentrations and adjust dosage as necessary. (See Elimination: Special Populations, under Pharmacokinetics.)

Geriatric Patients

No specific dosage recommendations. (See Geriatric Use under Cautions.)


Dosage adjustments may be required.

Cautions for Insulin Glulisine





Most common adverse effect of insulins. Blood glucose concentration monitoring is recommended for all diabetic patients. Hypoglycemic timing may differ among various insulin formulations and may change when the treatment regimen or timing of dosing of the insulins is changed.

Rapid changes in serum glucose concentrations may precipitate manifestations of hypoglycemia, regardless of glucose concentrations. Early warning signs of hypoglycemia may be diminished or absent in patients with long-standing diabetes mellitus, diabetic neuropathy, intensified diabetes control, and/or those receiving drugs such as β-adrenergic blocking agents that mask catecholamine-induced manifestations of hypoglycemia. Severe hypoglycemia (including loss of consciousness) may occur prior to patient’s awareness.

Use intensive insulin therapy with caution in patients with a history of hypoglycemic unawareness or recurrent, severe hypoglycemic episodes. Higher target blood glucose concentrations (e.g., fasting blood glucose concentrations of 140 mg/dL and 2-hour postprandial concentrations of 200–250 mg/dL) are advisable in these patients.

Insulin Pumps

For solution and drug compatibility information, see Compatibility under Stability. For pump compatibility, see Sub-Q Infusion under Administration in Dosage and Administration.

Because of rapid onset and shorter duration of action of insulin glulisine compared to insulin human, risk of hyperglycemia and ketosis in a shorter time period if pump or infusion set malfunctions or if insulin degradation occurs.

Prompt identification and correction of hyperglycemia or ketosis is necessary; may require interim therapy with sub-Q injections until problems with pump are corrected.

Sensitivity Reactions

Hypersensitivity Reactions

Possible localized allergic reactions (e.g., pruritus, erythema, swelling) at injection site; usually resolve within a few days to a few weeks. In some patients, may be related to other factors (e.g., irritants in skin cleaning agent, poor injection technique).

Generalized hypersensitivity reactions (e.g., rash, pruritus, shortness of breath, wheezing, hypotension, tachycardia, diaphoresis, anaphylaxis) reported less frequently than localized reactions, but may be life-threatening.

Localized reactions and generalized myalgias reported with use of m-cresol, an excipient in the formulation.

Antibody Formation

Can stimulate transient formation of antibodies to insulin that may cross-react with insulin glulisine or HbA1c insulin human. No correlation found between antibody concentration and changes in HbA1c, insulin doses, or incidence of hypoglycemia.

General Precautions

Hypoglycemia and Hypokalemia

Following IV administration, closely monitor glucose and potassium concentrations to avoid potentially fatal hypoglycemia or hypokalemia. (See Hypoglycemia under Cautions.)


Atrophy or hypertrophy of subcutaneous fat tissue may occur at injection sites and may delay insulin absorption; injection site rotation may reduce or prevent these effects.

Specific Populations


Category C.


Not known whether insulin glulisine is distributed into milk; use caution in nursing women.

Pediatric Use

Safety and efficacy not established in children <18 years of age. (See Absorption: Special Populations, under Pharmacokinetics.)

Geriatric Use

No substantial differences in safety and efficacy in those ≥65 years of age relative to younger adults; however, possibility exists of greater sensitivity in some geriatric individuals.

Common Adverse Effects

Hypoglycemia, systemic hypersensitivity, injection site reaction.

Drug Interactions

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

Specific Drugs

Drugs That May Potentiate Hypoglycemic Effects17

ACE inhibitors


Fibrate derivatives


MAO inhibitors

Oral antidiabetic agents




Sulfa anti-infectives

Drugs That May Antagonize Hypoglycemic Effects17

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





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


HIV protease inhibitors




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

Thyroid hormones

Drugs That May Have a Variable Effect on Glycemic Control17

β-Adrenergic blocking agents



Lithium salts


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

β-Adrenergic blocking agents




Insulin Glulisine Pharmacokinetics



Following sub-Q injection, absorption is rapid; faster than that of insulin human (regular).

Following sub-Q injection, absolute bioavailability is approximately 70%.

Substantial interindividual and intraindividual variation may occur based on site of injection, method of administration, tissue blood supply, temperature, and physical activity.

Atrophy or hypertrophy of subcutaneous fat tissue at the injection site may delay absorption.


Following sub-Q injection, insulin glulisine has shorter onset of action than insulin human (regular).


Following sub-Q injection, duration is shorter than that of insulin human insulin (regular).

Special Populations

Relative differences in pharmacokinetics between insulin glulisine and insulin human (regular) in type 1 diabetic children 7–16 years of age similar to the relative differences observed in adults. (See Pediatric Use under Cautions.)



Following IV administration, distribution similar to that of insulin human (regular).

Not known whether insulin glulisine is distributed into milk.


Following sub-Q injection, elimination more rapid than that of insulin human (regular).

Following IV administration, elimination similar to that of human insulin (regular).


Sub-Q administration: 42 minutes.

IV administration: 13 minutes.

Special Populations

Reduced clearance reported in nondiabetic patients with moderate or severe renal impairment. (See Renal Impairment under Dosage and Administration.)

Effects of hepatic impairment not evaluated; however, possible increased circulating concentrations of insulin, reduced capacity for gluconeogenesis, and reduced insulin metabolism, based on observations with other insulins in patients with hepatic dysfunction. (See Hepatic Impairment under Dosage and Administration.)





Unopened vials and cartridges: 2–8°C. Protect from light. Do not freeze; discard if solution has been frozen.

Opened (in-use) vials: <25°C for ≤28 days. Protect from direct heat and light.

When diluted for IV administration, stable at room temperature for 48 hours.

OptiClik opened cartridges: <25°C away from direct heat and light. Discard opened cartridge system after 28 days. Do not refrigerate OptiClik system, with or without cartridges.

Infusion sets (reservoirs, tubing, and catheters): Discard infusion set and any insulin glulisine in the reservoir after 48 hours (or less) of use. Discard if exposed to >37°C.



When used in an external infusion pump, do not mix insulin glulisine with other insulins or diluents.

Manufacturer recommends use of polyvinyl chloride Viaflex infusion bags and polyvinyl chloride tubing with a dedicated infusion line; compatibility with other bags or tubing has not been established.

Solution Compatibility

Compatible with 0.9% sodium chloride injection.

Incompatible with dextrose or Ringer’s injection; other IV diluents not studied and not recommended.

Drug Compatibility

Compatible with isophane insulin human; incompatible with other insulin preparations.

If mixed with isophane insulin human for sub-Q injection, draw insulin glulisine into the syringe first. Administer immediately after mixing; do not administer such mixtures IV.


Advice to Patients


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


Dosage Forms


Brand Names




100 units/mL

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


AHFS DI Essentials™. © Copyright 2024, Selected Revisions July 1, 2008. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

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