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Insulin Glulisine

Pronunciation

(IN soo lin gloo LIS een)

Index Terms

  • Glulisine Insulin

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution, Injection:

Apidra: 100 units/mL (10 mL) [contains metacresol]

Solution Pen-injector, Subcutaneous:

Apidra SoloStar: 100 units/mL (3 mL) [contains metacresol]

Brand Names: U.S.

  • Apidra
  • Apidra SoloStar

Pharmacologic Category

  • Insulin, Rapid-Acting

Pharmacology

Insulin acts via specific membrane-bound receptors on target tissues to regulate metabolism of carbohydrate, protein, and fats. Target organs for insulin include the liver, skeletal muscle, and adipose tissue.

Within the liver, insulin stimulates hepatic glycogen synthesis. Insulin promotes hepatic synthesis of fatty acids, which are released into the circulation as lipoproteins. Skeletal muscle effects of insulin include increased protein synthesis and increased glycogen synthesis. Within adipose tissue, insulin stimulates the processing of circulating lipoproteins to provide free fatty acids, facilitating triglyceride synthesis and storage by adipocytes; also directly inhibits the hydrolysis of triglycerides. In addition, insulin stimulates the cellular uptake of amino acids and increases cellular permeability to several ions, including potassium, magnesium, and phosphate. By activating sodium-potassium ATPases, insulin promotes the intracellular movement of potassium.

Normally secreted by the pancreas, insulin products are manufactured for pharmacologic use through recombinant DNA technology using either E. coli or Saccharomyces cerevisiae. Insulin glulisine differs from human insulin by containing a lysine and glutamic acid at positions B3 and B29, respectively, in comparison to the asparagine and lysine found at B3 and B29 in human insulin. Insulins are categorized based on the onset, peak, and duration of effect (eg, rapid-, short-, intermediate-, and long-acting insulin). Insulin glulisine is a rapid-acting insulin analog.

Distribution

IV: 13 L

Excretion

Urine

Onset of Action

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

Time to Peak

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

Duration of Action

3-4 hours

Half-Life Elimination

IV: 13 minutes

SubQ: 42 minutes

Special Populations: Renal Function Impairment

Insulin clearance may be reduced in patients with impaired renal function.

Special Populations Note

Obesity: Tmax occurs faster and Cmax is greater with insulin glulisine compared with regular human insulin in obese patients.

Use: Labeled Indications

Treatment of type 1 diabetes mellitus (insulin dependent, IDDM) and type 2 diabetes mellitus (noninsulin dependent, NIDDM) to improve glycemic control

Use: Unlabeled

Hyperglycemia during critical illness

Contraindications

Hypersensitivity to insulin glulisine or any component of the formulation; during episodes of hypoglycemia

Dosing: Adult

Diabetes mellitus: Note: Insulin glulisine is a rapid-acting insulin analog which is normally administered SubQ as a premeal component of the insulin regimen or as a continuous SubQ infusion and should be used with an intermediate- or long-acting insulin. When compared to insulin regular, insulin glulisine has a more rapid onset and shorter duration of activity. In carefully controlled clinical settings with close medical supervision and monitoring of blood glucose and potassium, insulin glulisine may be administered IV. Insulin requirements vary dramatically between patients and dictate frequent monitoring and close medical supervision.

Diabetes mellitus, type 1: SubQ:

General insulin dosing:

Type 1: Note: Multiple daily doses or continuous subcutaneous infusions guided by blood glucose monitoring are the standard of diabetes care. Combinations of insulin formulations are commonly used. The daily doses presented below are expressed as the total units/kg/day of all insulin formulations combined.

Initial total insulin dose: 0.2 to 0.6 units/kg/day in divided doses. Conservative initial doses of 0.2 to 0.4 units/kg/day are often recommended to avoid the potential for hypoglycemia. A rapid-acting insulin may be the only insulin formulation used initially.

Usual maintenance range: 0.5 to 1 units/kg/day in divided doses. An estimate of anticipated needs may be based on body weight and/or activity factors as follows:

Nonobese: 0.4 to 0.6 units/kg/day

Obese: 0.8 to 1.2 units/kg/day

Pubescent Children and Adolescents: During puberty, requirements may substantially increase to >1 unit/kg/day and in some cases up to 2 units/kg/day (IDF-ISPAD 2011).

Division of daily insulin requirement ("conventional therapy"): Generally, 50% to 75% of the total daily dose (TDD) is given as an intermediate- or long-acting form of insulin (in 1 to 2 daily injections). The remaining portion of the TDD is then divided and administered before or at mealtimes (depending on the formulation) as a rapid-acting insulin (eg, insulin glulisine) or short-acting form of insulin. Some patients may benefit from the use of CSII which delivers rapid-acting insulin (insulin aspart) as a continuous infusion throughout the day and as boluses at mealtimes via an external pump device.

Division of daily insulin requirement ("intensive therapy"): Basal insulin delivery with 1 or 2 doses of intermediate- or long-acting insulin formulations superimposed with doses of short- or rapid-acting insulin (eg, insulin glulisine) formulations 3 or more times daily.

Adjustment of dose: Dosage must be titrated to achieve glucose control and avoid hypoglycemia. Adjust dose to maintain premeal and bedtime glucose in target range. Since combinations of agents are frequently used, dosage adjustment must address the individual component of the insulin regimen which most directly influences the blood glucose value in question, based on the known onset and duration of the insulin component. Treatment and monitoring regimens must be individualized. Also see Additional Information or Pharmacotherapy Pearls.

Continuous SubQ insulin infusion (insulin pump): A combination of a "basal" continuous insulin infusion rate with preprogrammed, premeal bolus doses which are patient controlled. When converting from multiple daily SubQ doses of maintenance insulin, it is advisable to reduce the basal rate to less than the equivalent of the total daily units of the longer-acting insulin (eg, NPH); divide the total number of units by 24 to get the basal rate in units/hour. Do not include the total units of regular insulin or other rapid-acting insulin formulations in this calculation. The same premeal regular insulin dosage may be used.

Diabetes mellitus, type 2: SubQ:

General considerations for insulin use in type 2 diabetes:

Timing of initiation: The goal of therapy is to achieve an HbA1c <7%. According to a position statement by the ADA and European Association for the Study of Diabetes (EASD), dual therapy (metformin + a second antihyperglycemic agent) is recommended in patients with type 2 diabetes who fail to achieve glycemic goals after ~3 months with lifestyle interventions and metformin monotherapy (unless contraindications to metformin exist). Preference is not given for adding insulin or a noninsulin agent as the second antihyperglycemic agent (drug choice should be individualized based on patient characteristics). However, insulin should be considered as part of a combination regimen when hyperglycemia is severe, particularly if patient is symptomatic or has catabolic features (eg, weight loss, ketosis). If insulin is selected, the addition of basal insulin (ie, a long-acting insulin such as glargine or detemir [not insulin glulisine]) is recommended. If HbA1c target not achieved after ~3 months of dual therapy, may proceed to triple therapy (Inzucchi 2015).

Intensification of therapy: If HbA1c target has not been met, despite titrating basal insulin (ie, long-acting insulin) to provide acceptable fasting blood glucose concentrations, intensification of therapy should be considered to cover postprandial glucose excursions. Options include adding a GLP-1 receptor agonist (eg, exenatide, liraglutide) or adding a mealtime insulin (1 injection of a rapid-acting insulin analog [lispro, aspart, glulisine]) initiated at a dose of 4 units or 0.1 units/kg or 10% basal dose before largest meal; may progress to “basal-bolus” dosing of 3 injections of a rapid-acting insulin analog [lispro, aspart, glulisine] per meal or dose by adding up the total current insulin dose, and provide one-half of this amount as basal and one-half as mealtime insulin (split evenly between 3 meals). Alternatively, although less studied, may transition from basal insulin (ie, long-acting insulin) to a twice daily premixed (or biphasic) insulin analog (70/30 aspart mix, 75/25 or 50/50 lispro mix) (Inzucchi 2015).

Hyperglycemia, critically ill (off-label use): IV continuous infusion: Insulin therapy should be implemented when blood glucose ≥150 mg/dL with a goal to maintain blood glucose <150 mg/dL (with values absolutely <180 mg/dL) using a protocol that achieves a low rate of hypoglycemia (ie, ≤70 mg/dL). Before discontinuation, stable ICU patients should be transitioned to a protocol-driven basal/bolus insulin regimen, based on insulin infusion history and carbohydrate intake, to avoid loss of glycemic control. Subcutaneous insulin therapy may be considered for selected clinically stable ICU patients (SCCM [Jacobi 2012]). Note: The Surviving Sepsis Campaign guidelines recommend initiating insulin dosing in patients with severe sepsis when 2 consecutive blood glucose concentrations are >180 mg/dL and to target an upper blood glucose ≤180 mg/dL (Dellinger 2013).

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

Diabetes mellitus, type 1: Children ≥4 years and Adolescents: Refer to adult dosing.

Dosing: Renal Impairment

No dosage adjustment provided in manufacturer’s labeling; insulin requirements may be reduced due to changes in insulin clearance or metabolism; monitor blood glucose closely.

Dosing: Hepatic Impairment

No dosage adjustment provided in manufacturer’s labeling; insulin requirements may be reduced due to changes in insulin clearance or metabolism; monitor blood glucose closely.

Dosing: Obesity

Refer to indication-specific dosing for obesity-related information (may not be available for all indications).

Reconstitution

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

Administration

SubQ administration: Do not use if solution is viscous or cloudy; use only if clear and colorless. Insulin glulisine should be administered within 15 minutes before or within 20 minutes after starting a meal. Cold injections should be avoided. SubQ administration is usually made into the thighs, arms, buttocks, or abdomen; rotate injection sites within the same region to avoid lipodystrophy. When mixing insulin glulisine with other preparations of insulin (eg, insulin NPH), insulin glulisine should be drawn into syringe first. Do not mix other insulin formulations with insulin glulisine contained in a cartridge or prefilled pen.

CSII administration: Do not use if solution is viscous or cloudy; use only if clear and colorless. Patients should be trained in the proper use of their external insulin pump and in intensive insulin therapy. Infusion sets, reservoirs, and infusion set insertion sites should be changed every 48 hours; rotate infusion sites. Do not dilute or mix other insulin formulations with insulin glulisine that is to be used in an external insulin pump.

IV administration: Do not use if solution is viscous or cloudy; use only if clear and colorless. May be administered IV with close monitoring of blood glucose and serum potassium; appropriate medical supervision is required. Do not administer insulin mixtures intravenously.

IV infusions: To minimize insulin adsorption to plastic IV tubing: Although data is lacking regarding adsorption with insulin glulisine, insulin regular loss has been shown to occur by adsorption to plastic (ie, PVC, polyethylene, polyolefin, polypropylene) IV containers and tubing (Greenwood 2012; Hirsch 1977; Hirsch 1981; Rocchio 2013; Thompson 2012). Therefore, flush the IV tubing with a priming infusion of 20 mL from the insulin infusion, whenever a new IV tubing set is added to the insulin infusion container (SCCM [Jacobi 2012]; Thompson 2012).

Note: Also refer to institution-specific protocols where appropriate.

Because of insulin adsorption to plastic IV tubing or infusion bags, the actual amount of insulin being administered via IV infusion could be substantially less than the apparent amount. Therefore, adjustment of the IV infusion rate should be based on effect and not solely on the apparent insulin dose. The apparent dose may be used as a starting point for determining the subsequent SubQ dosing regimen (Moghissi, 2009); however, the transition to SubQ administration requires continuous medical supervision, frequent monitoring of blood glucose, and careful adjustment of therapy. In addition, SubQ insulin should be given 1 to 4 hours prior to the discontinuation of IV insulin to prevent hyperglycemia (Moghissi, 2009).

Dietary Considerations

Individualized medical nutrition therapy (MNT) based on ADA recommendations is an integral part of therapy.

Compatibility

Stable in NS; incompatible with dextrose solution and Ringer's solution

Compatibility in syringe: Incompatible with insulin aspart, insulin detemir, insulin glargine, insulin lispro, insulin regular.

Storage

Unopened vials, cartridges, and prefilled pens may be stored under refrigeration between 2°C and 8°C (36°F to 46°F) until the expiration date or at room temperature for 28 days; do not freeze; keep away from heat and sunlight. Once punctured (in use), vials may be stored under refrigeration or at room temperature ≤25°C (≤77°F); use within 28 days. Cartridges and prefilled pens that have been punctured (in use) should be stored at temperatures ≤25°C (≤77°F) and used within 28 days; do not freeze or refrigerate. When used for CSII, insulin glulisine contained within an external insulin pump reservoir should be replaced every 48 hours; discard if exposed to temperatures >37°C (>98.6°F).

For IV infusion: Stable in NS for 48 hours at room temperature.

Drug Interactions

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

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

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

Adverse Reactions

>10%

Endocrine & metabolic: Severe hypoglycemia (1% to 8%; children and adolescents, type 1 diabetes: 16%)

Respiratory: Nasopharyngitis (8% to 11%), upper respiratory tract infection (7% to 11%)

1% to 10%

Cardiovascular: Peripheral edema (8%; adults, type 2 diabetes), hypertension (4%; adults, type 2 diabetes)

Central nervous system: Headache (7%; children and adolescents, type 1 diabetes), hypoglycemic seizure (6%; children and adolescents, type 1 diabetes)

Endocrine & metabolic: Hypoglycemia (7%; adults, type 1 diabetes)

Hypersensitivity: Hypersensitivity reaction (4%)

Infection: Influenza (4% to 6%)

Local: Infusion site reaction (10%)

Neuromuscular & skeletal: Arthralgia (6%; adults, type 2 diabetes)

Frequency not defined:

Dermatologic: Pruritus, skin rash

Endocrine & metabolic: Hypokalemia, weight gain

Hypersensitivity: Anaphylaxis

Immunologic: Antibody development (no effect on drug efficacy)

Local: Hypertrophy at injection site, lipoatrophy at injection site

<1% (Limited to important or life-threatening): Catheter complication

Warnings/Precautions

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.

Monitoring Parameters

Critically ill patients receiving insulin infusion: Blood glucose every 1-2 hours. Note: Every 4 hour blood glucose monitoring is not recommended unless a low hypoglycemia rate is demonstrated with the insulin protocol used. Arterial or venous whole blood sampling is recommended for patients in shock, on vasopressor therapy, or with severe edema, and when on a prolonged insulin infusion (SCCM [Jacobi 2012]).

Diabetes mellitus: Plasma glucose, electrolytes, HbA1c (at least twice yearly in patients who have stable glycemic control and are meeting treatment goals; quarterly in patients not meeting treatment goals or with therapy change [ADA 2016a])

IV administration: Close monitoring of blood glucose and serum potassium

Pregnancy Risk Factor

C

Pregnancy Considerations

In animal reproduction studies, outcomes were similar to those observed with regular insulin.

In women with diabetes, maternal hyperglycemia can be associated with congenital malformations as well as adverse effects in the fetus, neonate, and the mother (ACOG 2005; ADA 2016d; Kitzmiller 2008; Metzger 2007). To prevent adverse outcomes, prior to conception and throughout pregnancy maternal blood glucose and HbA1c should be kept as close to target goals as possible but without causing significant hypoglycemia (ACOG 2013; ADA 2016d; Blumer 2013; Kitzmiller 2008; Lambert 2013). Prior to pregnancy, effective contraception should be used until glycemic control is achieved (ADA 2016d; Kitzmiller 2008).

Insulin requirements tend to fall during the first trimester of pregnancy and increase in the later trimesters, peaking at 28 to 32 weeks of gestation. Following delivery, insulin requirements decrease rapidly (ACOG 2005).

Due to lack of clinical data, insulin glulisine is not currently recommended for use in pregnant women (Blumer 2013).

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Have patient report immediately to prescriber signs of low blood sugar (dizziness, headache, fatigue, feeling weak, shaking, a fast heartbeat, confusion, hunger, or sweating), signs of low potassium (muscle pain or weakness, muscle cramps, or an abnormal heartbeat), severe injection site irritation, vision changes, chills, severe dizziness, passing out, mood changes, nightmares, insomnia, seizures, slurred speech, burning or numbness feeling, abnormal gait, shortness of breath, excessive weight gain, swelling of arms or legs, or change in skin to thick or thin at injection site (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.

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