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Special Alerts
Insulin Glargine: Potential Association With Increased Cancer Risk - July 1, 2009
The U.S. Food and Drug Administration (FDA) has issued a notification to healthcare providers and their patients regarding a possible increased risk of cancer associated with insulin glargine (Lantus®). Three recently-published observational studies describe a potential association between insulin glargine and certain types of cancer (Colhoun, 2009; Hemkens, 2009; Jonasson, 2009); whereas a fourth study failed to produce similar results (Currie, 2009). The FDA is currently reviewing safety data for insulin glargine from completed and ongoing clinical trials as well as the recently-published observational studies. Until more information is known, the FDA recommends that patients not discontinue their insulin glargine without consulting their physician due to the serious health risks that accompany uncontrolled hyperglycemia.
For more information, U.S. healthcare professionals may refer to the following FDA website: http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm170089.htm
References:
Colhoun HM, “Use of Insulin Glargine and Cancer Incidence in Scotland: A Study from the Scottish Diabetes Network Epidemiology Group,” Diabetologia, 2009. Available at: http://webcast.easd.org/press/glargine/download/090818Colhounacceptedpaperadjusted.pdf
Currie CJ, Poole CD, and Gale EAM, “The Influence of Glucose-Lowering Therapies on Cancer Risk in Type 2 Diabetes,” Diabetologia, 2009. Available at: http://webcast.easd.org/press/glargine/download/090740Currie2ndproofs.pdf
Hemkens LG, Grouven U, Bender R, et al, “Risk of Malignancies in Patients With Diabetes Treated With Human Insulin or Insulin Analogues: A Cohort Study,” Diabetologia, 2009, available at: http://www.diabetologia-journal.org/cancer_files/081131Hemkenscorrectedproofs.pdf
Jonasson JM, Ljung R, Talback M, et al, “Insulin Glargine Use and Short-Term Incidence of Malignancies - A Population-Based Follow-up Study in Sweden,” Diabetologia, 2009. Available at: http://www.diabetologia-journal.org/cancer_files/090776Jonassonacceptedpaper.pdf
Insulin Pens: Sharing Results in Cross-Contamination - March 19, 2009
The U.S. Food and Drug Administration (FDA) has issued a warning to healthcare providers and their patients regarding the sharing of insulin pens and cartridges among patients. This practice may result in transmission of a number of pathogens including hepatitis, HIV, and other blood-borne pathogens and should be abandoned. Insulin pens are FDA-approved for single-patient use only.
For more information, U.S. healthcare professionals may refer to the following FDA website: http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm127783.htm
Medication Safety Issues
Sound-alike/look-alike issues:
Insulin glargine may be confused with insulin glulisine
Lantus® may be confused with latanoprost, Xalatan®
High alert medication: The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drugs which have a heightened risk of causing significant patient harm when used in error.
Due to the number of insulin preparations, it is essential to identify/clarify the type of insulin to be used.
Note: Insulin glargine is a clear solution, but it is NOT intended for I.V. or I.M. administration.
Cross-contamination may occur if insulin pens are shared among multiple patients. Steps should be taken to prohibit sharing of insulin pens.
Pronunciation
(IN soo lin GLAR jeen)
U.S. Brand Names
Index Terms
Generic Available
No
Canadian Brand Names
Pharmacologic Category
Pharmacologic Category Synonyms
Use: Labeled Indications
Treatment of type 1 diabetes mellitus (insulin dependent, IDDM) and type 2 diabetes mellitus (noninsulin dependent, NIDDM) to improve glycemic control
Pregnancy Risk Factor
C
Pregnancy Considerations
Adverse events have been shown in some animal studies; therefore, the manufacturer classifies insulin glargine as pregnancy category C. Maternal hyperglycemia can be associated with adverse effects in the fetus, including macrosomia, neonatal hyperglycemia, and hyperbilirubinemia; the risk of congenital malformations is increased when Hb A1c is above the normal range.Insulin requirements tend to fall during the first trimester of pregnancy and increase in the later trimesters, peaking at 28-32 weeks of gestation. Following delivery, insulin requirements decrease rapidly. Diabetes can be associated with adverse effects in the mother. Poorly-treated diabetes may cause end-organ damage that may in turn negatively affect obstetric outcomes. Physiologic glucose levels should be maintained prior to and during pregnancy to decrease the risk of adverse events in the fetus and the mother. Insulin is the drug of choice for the control of diabetes mellitus during pregnancy. Pregnancy outcome information following the use of insulin glargine is available from case reports and small studies. Current reports indicate that insulin glargine is effective when used during pregnancy and may be an option for pregnant women with significantly uncontrolled diabetes; however, pregnant women using insulin glargine should be switched to NPH insulin pending additional safety information with this agent.
Lactation
Excretion in breast milk unknown/compatible
Breast-Feeding Considerations
It is not known if significant amounts of insulin glargine are found in breast milk. Endogenous insulin can be found in breast milk. Plasma glucose concentrations in the mother affect glucose concentrations in breast milk. The gastrointestinal tract destroys insulin when administered orally; therefore, insulin is not expected to be absorbed intact by the breast-feeding infant. All types of insulin are safe for use while breast-feeding. Due to increased calorie expenditure, women with diabetes may require less insulin while nursing.
Contraindications
Hypersensitivity to insulin glargine or any component of the formulation
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.
• Hypokalemia: Insulin (especially I.V. 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 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.
Dosage form specific issues:
• Product variation: Human insulin differs from animal-source insulin. Any change of insulin should be made cautiously; changing manufacturers, type, and/or method of manufacture may result in the need for a change of dosage.
Other warnings/precautions:
• Administration: Insulin glargine is a clear solution, but it is NOT intended for I.V. or I.M. administration.
• 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 subcutaneous insulin infusion [CSII]) and/or preprandial insulin (eg, short- or rapid-acting insulin) (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.
• Patient education: Diabetes self-management education (DSME) is essential to maximize the effectiveness of therapy.
Adverse Reactions
Refer to Insulin Regular.
Metabolism/Transport Effects
Refer to Insulin Regular.
Drug Interactions
Antidiabetic Agents (Thiazolidinedione): Insulin may enhance the fluid-retaining effect of Antidiabetic Agents (Thiazolidinedione). Risk C: Monitor therapy
Beta-Blockers: May enhance the hypoglycemic effect of Insulin. Exceptions: Levobunolol; Metipranolol. Risk C: Monitor therapy
Corticosteroids (Orally Inhaled): May diminish the hypoglycemic effect of Antidiabetic Agents. In some instances, corticosteroid-mediated HPA axis suppression has led to episodes of acute adrenal crisis, which may manifest as enhanced hypoglycemia, particularly in the setting of insulin or other antidiabetic agent use. Risk C: Monitor therapy
Corticosteroids (Systemic): May diminish the hypoglycemic effect of Antidiabetic Agents. In some instances, corticosteroid-mediated HPA axis suppression has led to episodes of acute adrenal crisis, which may manifest as enhanced hypoglycemia, particularly in the setting of insulin or other antidiabetic agent use. Risk C: Monitor therapy
Edetate CALCIUM Disodium: May enhance the hypoglycemic effect of Insulin. Risk C: Monitor therapy
Edetate Disodium: May enhance the hypoglycemic effect of Insulin. Risk C: Monitor therapy
Herbs (Hypoglycemic Properties): May enhance the hypoglycemic effect of Hypoglycemic Agents. Risk C: Monitor therapy
Hypoglycemic Agents: May enhance the adverse/toxic effect of other Hypoglycemic Agents. Risk C: Monitor therapy
Luteinizing Hormone-Releasing Hormone Analogs: May diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapy
Pegvisomant: May enhance the hypoglycemic effect of Antidiabetic Agents. Risk C: Monitor therapy
Quinolone Antibiotics: Insulin may enhance the hyperglycemic effect of Quinolone Antibiotics. Insulin may enhance the hypoglycemic effect of Quinolone Antibiotics. Risk C: Monitor therapy
Somatropin: May diminish the hypoglycemic effect of Antidiabetic Agents. Risk D: Consider therapy modification
Thiazide Diuretics: May diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapy
Ethanol/Nutrition/Herb Interactions
Refer to 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 <30°C (<86°F) 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 <30°C (<86°F); use within 28 days. Cartridges within the OptiClik® system and prefilled pens (SoloStar®) that have been punctured (in use) should be stored at temperatures <30°C (<86°F) and used within 28 days; do not freeze or refrigerate.
Compatibility
Compatibility in syringe: Incompatible: Insulin aspart, insulin detemir, insulin glulisine, insulin lispro, insulin NPH, and insulin regular.
Mechanism of Action
Insulin glargine is a long-acting insulin analog.
Refer to Insulin Regular.
Pharmacodynamics/Kinetics
Note: Rate of absorption, onset, and duration of activity may be affected by site of injection, exercise, presence of lipodystrophy, local blood supply, and/or temperature.
Onset of action: 3-4 hours
Peak effect: No pronounced peak
Duration: Generally 24 hours or longer; reported range: 10.8 to >24 hours (up to 32 hours documented in some studies)
Absorption: Slow; upon injection into the subcutaneous tissue, microprecipitates form which allow small amounts of insulin glargine to release over time
Metabolism: Partially metabolized in the skin to form two active metabolites
Time to peak, plasma: No pronounced peak
Excretion: Urine
Dosage
Note: Insulin glargine is approximately equipotent to human insulin, but has a slower onset, no pronounced peak, and a longer duration of activity.
SubQ: Diabetes mellitus:
Type 1:
Children <6 years (unlabeled use): Refer to Insulin Regular
Children ?6 years and Adults: Refer to Insulin Regular
Type 2:
Children (unlabeled use): Refer to Insulin Regular
Adults: Refer to Insulin Regular
Dosage adjustment in renal impairment: Refer to Insulin Regular
Dosage adjustment in hepatic impairment: Refer to Insulin Regular
Administration: Other
SubQ administration: Do not use if solution is viscous or cloudy; use only if clear and colorless with no visible particles. Insulin glargine should be administered once daily, at any time of day; however, administer at the same time each day. Cold injections should be avoided. SubQ administration is usually made into the thighs, arms, buttocks, or abdomen; rotate injection sites. Do not dilute or mix insulin glargine with any other insulin formulation or solution.
Monitoring Parameters
Diabetes mellitus: Plasma glucose, electrolytes, Hb A1c
Reference Range
Refer to Insulin Regular.
Dietary Considerations
Individualized medical nutrition therapy (MNT) based on ADA recommendations is an integral part of therapy.
Patient Education
Do not take any new medication during therapy unless approved by prescriber. Do not share pens, cartridges, or needles with others. This medication is used to control diabetes; it is not a cure. It is imperative to follow other components of prescribed treatment (eg, diet and exercise regimen). Take exactly as directed. Do not change dose or discontinue unless advised by prescriber. If you experience hypoglycemic reaction, contact prescriber immediately. Always carry quick source of sugar with you. Monitor glucose levels as directed by prescriber. Report adverse side effects, including chest pain or palpitations; persistent fatigue, confusion, headache; skin rash or redness; numbness of mouth, lips, or tongue; muscle weakness or tremors; vision changes; respiratory difficulty; or nausea, vomiting, or flu-like symptoms. Pregnancy/breast-feeding precautions: Inform prescriber if you are or intend to become pregnant. Consult prescriber if breast-feeding.
Geriatric Considerations
Intensive glucose control (Hb A1c <6.5) has been linked to increased all cause and cardiovascular mortality, hypoglycemia requiring assistance, and weight gain in adult type 2 diabetes. For elderly patients with diabetes who are relatively healthy, attaining target goals for aspirin use, blood pressure, lipids, smoking cessation, and diet and exercise may be more important than normalized glycemic control.
Additional Information
The duration of action of insulin glargine is generally 24 hours or longer with a relatively flat action profile throughout this interval. Many pharmacokinetic and pharmacodynamic studies were terminated at 24 hours despite the fact that insulin glargine continued to exhibit hypoglycemic activity beyond 24 hours; therefore, it is difficult to determine the absolute duration of action.
Clinicians should be aware that, in rare cases, patients may exhibit hypoglycemic activity beyond 24 hours and that accumulation of insulin glargine is possible. Adequate monitoring and subsequent dosage adjustments should be made in patients who are requiring less insulin to maintain euglycemia after several days of therapy.
On the other hand, insulin glargine has a reported duration of action that ranges from 10.8 to >24 hours. On rare occasions, patients may require twice-daily injections of insulin glargine to deliver adequate basal insulin coverage over 24 hours. Some clinicians may also switch to twice-daily dosing in patients who require >100 units of insulin glargine per day to allow for complete absorption. Dosing insulin glargine 3 times daily is not recommended.
Also, refer to Insulin Regular.
Dental Health: Effects on Dental Treatment
Patients with type 1 diabetes (insulin dependent) should be appointed for dental treatment in the morning in order to minimize chance of stress-induced hypoglycemia.
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Mental Health: Effects on Mental Status
May cause drowsiness or confusion
Mental Health: Effects on Psychiatric Treatment
MAO inhibitors may enhance the hypoglycemic effects of insulin; TCAs may antagonize the effects of insulin
Nursing: Physical Assessment/Monitoring
Assess potential for interactions with other prescriptions, OTC medications, or herbal products patient may be taking. Assess results of laboratory tests, therapeutic effectiveness, and adverse reactions (eg, hypoglycemia) at regular intervals during therapy. Teach patient proper use, including appropriate injection technique and syringe/needle disposal and monitoring requirements (or refer to diabetic educator), possible side effects/appropriate interventions, and adverse symptoms to report.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, solution:
Lantus®: 100 units/mL (3 mL) [OptiClik® prefilled cartridge or SoloStar® disposable insulin device]; (10 mL) [vial]
Pricing: U.S. (www.drugstore.com)
Solution (Lantus)
100 units/mL (10): $103.59
Solution (Lantus for OptiClik)
100 units/mL (15): $190.75
Solution (Lantus SoloStar)
100 units/mL (15): $187.61
References
Hamann A, Matthaei S, Rosack C, et al, “A Randomized Clinical Trial Comparing Breakfast, Dinner, or Bedtime Administration of Insulin Glargine in Patients With Type 1 Diabetes,” Diabetes Care, 2003, 26(6):1738-44.
Heinemann L, Hompesch B, Linkeschova R, et al, “Time-Action Profile of the Long-Acting Insulin Analog Insulin Glargine (HOE901) in Comparison With Those of NPH and Placebo,” Diabetes Care, 2000, 23(5):644-9.
Holman RR, Thorne KI, Farmer AJ, et al, “Addition of Biphasic, Prandial, or Basal Insulin to Oral Therapy in Type 2 Diabetes,” N Engl J Med, 2007, 357(17):1716-30.
Lepore M, Pampanelli S, Fanelli C, et al, “Pharmacokinetics and Pharmacodynamics of Subcutaneous Injection of Long-Acting Human Insulin Analog Glargine, NPH Insulin, and Ultralente Human Insulin and Continuous Subcutaneous Infusion of Insulin Lispro,” Diabetes, 2000, 49(12):2142-8.
Owens DR, Coates PA, Luzio SD, et al, “Pharmacokinetics of 125I-Labeled Insulin Glargine (HOE 901) in Healthy Men,” Diabetes Care, 2000, 23(6):813-9.
Porcellati F, Rossetti P, Ricci NB, et al, “Pharmacokinetics and Pharmacodynamics of the Long-Acting Insulin Analog Glargine After 1 Week of Use Compared With Its First Administration in Subjects With Type 1 Diabetes,” Diabetes Care, 2007, 30(5):1261-3.
Raskin P, Klaff L, Bergenstal R, et al, “A 16-Week Comparison of the Novel Insulin Analog Insulin Glargine (HOE901) and NPH Human Insulin Used With Insulin Lispro in Patients With Type 1 Diabetes,” Diabetes Care, 2000, 23(11):1666-71.
Ratner RE, Hirsch IB, Neifing JL, et al, “Less Hypoglycemia With Insulin Glargine in Intensive Insulin Therapy for Type 1 Diabetes. U.S. Study Group of Insulin Glargine in Type 1 Diabetes,” Diabetes Care, 2000, 23(5):639-43.
Riddle MC, Rosenstock J, and Gerich J, “The Treat-To-Target Trial,” Diabetes Care, 2003, 26(11):3080-6.
Rosenstock J, Schwartz SL, Clark CM Jr, et al, “Basal Insulin Therapy in Type 2 Diabetes,” Diabetes Care, 2001, 24(4):631-6.
Schober E, Schoenle E, Van Dyk J, et al, “Comparative Trial Between Insulin Glargine and NPH Insulin in Children and Adolescents With Type 1 Diabetes,” Diabetes Care, 2001, 24(11):2005-6.
Scholtz HE, Pretorius SG, Wessels DH, et al, “Pharmacokinetic and Glucodynamic Variability: Assessment of Insulin Glargine, NPH Insulin, and Insulin Ultralente in Healthy Volunteers Using a Euglycaemic Clamp Technique,” Diabetologia, 2005, 48(10):1988-95.
Yki-Jarvinen H, Dressler A, and Ziemen M, “Less Nocturnal Hypoglycemia and Better Post-Dinner Glucose Control With Bedtime Insulin Glargine Compared With Bedtime NPH Insulin During Insulin Combination Therapy in Type 2 Diabetes,” Diabetes Care, 2000, 23(8):1130-6.
International Brand Names
Lexi-Comp.com
Last full review/revision September 2009
Content last modified September 2009
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