Insulin Glulisine

Insulin glulisine 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 this insulin. 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 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

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 insulin glulisine.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-332-1088.

Do not take insulin glulisine:

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

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

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

Insulin glulisine 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 insulin glulisine 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 insulin 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.

Insulin can cause low blood sugar. Avoid driving or operating machinery until you know how this medicine will affect you.

Avoid medication errors by always checking the medicine label before injecting your insulin.

Avoid drinking alcohol. It can cause low blood sugar and may interfere with your diabetes treatment.

• Pharmacologic effects comparable to those of insulin human;1 8 stimulates peripheral glucose uptake by tissues (e.g., skeletal muscle, fat), inhibits hepatic glucose production, inhibits lipolysis, and enhances protein synthesis.1

• More rapid onset and shorter duration of action than insulin human (regular) following sub-Q administration.1 3 7 8

• Provide copy of manufacturer’s information for patients.1

• Importance of strict adherence to manufacturer's instructions regarding assembly, administration, and care of specialized delivery systems, such as insulin pens or pumps.1 2

• Provide instructions regarding self-monitoring of blood glucose, insulin storage and injection technique, adherence to meal planning, physical exercise, blood glucose monitoring, and management of hypoglycemia or hyperglycemia.1 2

• Importance of not mixing insulin glulisine for sub-Q injection with insulin preparations other than isophane insulin human.1 2 When mixing with isophane insulin human, importance of drawing insulin glulisine into the syringe first.1 2 8 Importance of using insulin glulisine only if solution is clear and colorless with no visible particles.1 2

• Importance of not mixing insulin glulisine with other insulins or diluents when used in external sub-Q infusion pumps.1 2

• Importance of administering insulin glulisine ≤15 minutes before a meal or ≤20 minutes after the start of a meal.1 2 8

• Importance of changing insulin dosage with caution and only under medical supervision.1 2 Discuss potential for alterations in insulin requirements in special situations (e.g., illness, emotional disturbances or other stresses, concomitant agents that alter glycemic control).1 2 Discuss potential for alterations in insulin requirements as a result of changes in physical activity, inadequate or missed doses, inadvertent administration of incorrect doses, inadequate food intake, or skipped meals.1 2 8

• Importance of providing instructions on safe disposal of needles.2

• Importance of informing clinicians of recurrent or persistent skin reactions (erythema, pruritus, thickened skin, skin depression or atrophy) at injection or infusion sites.1 2 Importance of selecting a new infusion or injection site if such reactions occur.1 2

• Importance of informing clinicians of the development of generalized hypersensitivity reactions (shortness of breath, low BP, wheezing, whole body rash, fast pulse, sweating).2

• Importance of wearing a medical alert identification bracelet or pendant, carrying ample insulin and supplies when traveling, and having carbohydrates (sugar or candy) on hand for emergencies.2

• Importance of resumption of sub-Q injections of insulin glulisine with a syringe and of contacting a clinician if pump malfunctions occur and cannot be corrected promptly.1 2

• Importance of contacting a clinician if self-monitored blood glucose concentrations are consistently high.2

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, vitamins, and herbal supplements, as well as concomitant alcohol ingestion.1 2

• Importance of informing clinicians of concomitant illnesses, including hepatic or renal disease.2

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1 2

• Importance of informing patients of other important precautionary information.1 (See Cautions.)

0.2-0.5 hours; Peak effect: 1.6-2.8 hours

Time to Peak

Plasma: 60 minutes (range: 40-120 minutes)

There are no dosage adjustments provided in the manufacturer's labeling; insulin requirements may be reduced due to changes in insulin clearance or metabolism; monitor blood glucose closely.

For IV infusion: May be diluted in NS to concentrations of 0.05-1 unit/mL.

Alpha-Lipoic Acid: May enhance the hypoglycemic effect of Antidiabetic Agents. Monitor therapy

Androgens: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Exceptions: Danazol. Monitor therapy

Antidiabetic Agents: May enhance the hypoglycemic effect of Hypoglycemia-Associated Agents. Monitor therapy

Beta-Blockers: May enhance the hypoglycemic effect of Insulin. Exceptions: Levobunolol; Metipranolol. Monitor therapy

DPP-IV Inhibitors: May enhance the hypoglycemic effect of Insulin. Management: Consider a decrease in insulin dose when initiating therapy with a dipeptidyl peptidase-IV inhibitor and monitor patients for hypoglycemia. Consider therapy modification

Edetate CALCIUM Disodium: May enhance the hypoglycemic effect of Insulin. Monitor therapy

Edetate Disodium: May enhance the hypoglycemic effect of Insulin. Monitor therapy

GLP-1 Agonists: May enhance the hypoglycemic effect of Insulin. Management: Consider insulin dose reductions when used in combination with glucagon-like peptide-1 agonists. Avoid the use of lixisenatide in patients receiving both basal insulin and a sulfonylurea. Exceptions: Liraglutide. Consider therapy modification

Guanethidine: May enhance the hypoglycemic effect of Antidiabetic Agents. Monitor therapy

Herbs (Hypoglycemic Properties): May enhance the hypoglycemic effect of Hypoglycemia-Associated Agents. Monitor therapy

Hyperglycemia-Associated Agents: May diminish the therapeutic effect of Antidiabetic Agents. Monitor therapy

Hypoglycemia-Associated Agents: May enhance the hypoglycemic effect of other Hypoglycemia-Associated Agents. Monitor therapy

Hypoglycemia-Associated Agents: Antidiabetic Agents may enhance the hypoglycemic effect of Hypoglycemia-Associated Agents. Monitor therapy

Liraglutide: May enhance the hypoglycemic effect of Insulin. Management: If liraglutide is used for the treatment of diabetes (Victoza), consider insulin dose reductions. The combination of liraglutide and insulin should be avoided if liraglutide is used exclusively for weight loss (Saxenda). Consider therapy modification

MAO Inhibitors: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Monitor therapy

Metreleptin: May enhance the hypoglycemic effect of Insulin. Management: Insulin dosage adjustments (including potentially large decreases) may be required to minimize the risk for hypoglycemia with concurrent use of metreleptin. Monitor closely. Consider therapy modification

Pegvisomant: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Monitor therapy

Pioglitazone: May enhance the adverse/toxic effect of Insulin. Specifically, the risk for hypoglycemia, fluid retention, and heart failure may be increased with this combination. Management: If insulin is combined with pioglitazone, dose reductions should be considered to reduce the risk of hypoglycemia. Monitor patients for fluid retention and signs/symptoms of heart failure. Consider therapy modification

Pramlintide: May enhance the hypoglycemic effect of Insulin. Management: Upon initiation of pramlintide, decrease mealtime insulin dose by 50% to reduce the risk of hypoglycemia. Monitor blood glucose frequently and individualize further insulin dose adjustments based on glycemic control. Consider therapy modification

Prothionamide: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Monitor therapy

Quinolone Antibiotics: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Quinolone Antibiotics may diminish the therapeutic effect of Blood Glucose Lowering Agents. Specifically, if an agent is being used to treat diabetes, loss of blood sugar control may occur with quinolone use. Monitor therapy

Rosiglitazone: Insulin may enhance the adverse/toxic effect of Rosiglitazone. Specifically, the risk of fluid retention, heart failure, and hypoglycemia may be increased with this combination. Avoid combination

Salicylates: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Monitor therapy

Selective Serotonin Reuptake Inhibitors: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Monitor therapy

SGLT2 Inhibitors: May enhance the hypoglycemic effect of Insulin. Management: Consider a decrease in insulin dose when initiating therapy with a sodium-glucose cotransporter 2 inhibitor and monitor patients for hypoglycemia. Consider therapy modification

Thiazide and Thiazide-Like Diuretics: May diminish the therapeutic effect of Antidiabetic Agents. Monitor therapy

Concerns related to adverse effects:

• Hypoglycemia: The most common adverse effect of insulin is hypoglycemia. The timing of hypoglycemia differs among various insulin formulations. Hypoglycemia may result from increased work or exercise without eating; use of long-acting insulin preparations (eg, insulin detemir, insulin glargine) may delay recovery from hypoglycemia. Profound and prolonged episodes of hypoglycemia may result in convulsions, unconsciousness, temporary or permanent brain damage or even death. Insulin requirements may be altered during illness, emotional disturbances or other stressors. Instruct patients to use caution with ethanol; may increase risk of hypoglycemia.

• Hypokalemia: Insulin (especially IV insulin) causes a shift of potassium from the extracellular space to the intracellular space, possibly producing hypokalemia. If left untreated, hypokalemia may result in respiratory paralysis, ventricular arrhythmia and even death. Use with caution in patients at risk for hypokalemia (eg, loop diuretic use). Monitor serum potassium frequently with IV use and supplement potassium when necessary.

Disease-related concerns:

• Hepatic impairment: Use with caution in patients with hepatic impairment. Dosage requirements may be reduced.

• Renal impairment: Use with caution in patients with renal impairment. Dosage requirements may be reduced.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Dosage form specific issues:

• Multiple dose injection pens: According to the Centers for Disease Control and Prevention (CDC), pen-shaped injection devices should never be used for more than one person (even when the needle is changed) because of the risk of infection. The injection device should be clearly labeled with individual patient information to ensure that the correct pen is used (CDC, 2012).

Other warnings/precautions:

• Appropriate use: Diabetes mellitus: The general objective of exogenous insulin therapy is to approximate the physiologic pattern of insulin secretion which is characterized by two distinct phases. Phase 1 insulin secretion suppresses hepatic glucose production and phase 2 insulin secretion occurs in response to carbohydrate ingestion; therefore, exogenous insulin therapy may consist of basal insulin (eg, intermediate- or long-acting insulin via continuous insulin infusion [CSII]) and/or preprandial insulin (eg, short- or rapid-acting insulin [eg, insulin glulisine]) (see Related Information: Insulin Products). Patients with type 1 diabetes do not produce endogenous insulin; therefore, these patients require both basal and preprandial insulin administration. Patients with type 2 diabetes retain some beta-cell function in the early stages of their disease; however, as the disease progresses, phase 1 insulin secretion may become completely impaired and phase 2 insulin secretion becomes delayed and/or inadequate in response to meals. Therefore, patients with type 2 diabetes may be treated with oral antidiabetic agents, basal insulin, and/or preprandial insulin depending on the stage of disease and current glycemic control. Since treatment regimens often consist of multiple agents, dosage adjustments must address the specific phase of insulin release that is primarily contributing to the patient's impaired glycemic control. Treatment and monitoring regimens must be individualized.

Due to the short duration of action of insulin glulisine, a longer acting insulin or CSII via an external insulin pump is needed to maintain adequate glucose control in patients with type 1 diabetes mellitus (insulin dependent, IDDM). In both type 1 and type 2 diabetes, preprandial administration of insulin glulisine should be immediately followed by a meal within 15 minutes.

• CSII administration: May be administered via CSII; do not dilute or mix with other insulin formulations. Rule out external pump failure if unexplained hyperglycemia or ketosis occurs; temporary SubQ insulin administration may be required until the problem is identified and corrected.

• IV administration: Insulin glulisine may be administered IV in selected clinical situations to control hyperglycemia; close monitoring of blood glucose and serum potassium as well as medical supervision is required.

• Patient education: Diabetes self-management education (DSME) is essential to maximize the effectiveness of therapy.