Generic Name: Insulin Glargine
Class: Insulins
ATC Class: A10AB01
VA Class: HS501
Chemical Name: 21A-Glycine-30Ba-l-arginine-30Bb-l-arginine insulin (human)
Molecular Formula: C267H404N72O78S6
CAS Number: 160337-95-1

Warning(s)

Special Alerts:

FDA notified healthcare professionals and patients that it is aware of four recently-published observational studies that looked at the use of insulin glargine (Lantus) and possible risk for cancer in patients with diabetes. Three of the four studies suggest an increased risk for cancer associated with use of insulin glargine. Based on the currently available data, the FDA recommends that patients should not stop taking their insulin therapy without consulting a physician, since uncontrolled blood sugar levels can have both immediate and long-term serious adverse effects.

FDA is currently reviewing many sources of safety data for insulin glargine, including these newly published observational studies, data from all completed controlled clinical trials, and information about ongoing controlled clinical trials, to better understand the risk, if any, for cancer associated with use of insulin glargine. Discussions are also ongoing between FDA and the manufacturer of insulin glargine as to whether any additional studies evaluating the safety and efficacy of this drug will need to be performed. FDA will communicate the results on its ongoing review to the public, as appropriate, as our review continues.

The FDA encourages both healthcare professionals and patients to report side effects from the use of insulin glargine to the FDA’s MedWatch Adverse Event Reporting Program. For more information visit the FDA website at: and .

Introduction

Long-acting human insulin analog;1 prepared using recombinant DNA technology and special laboratory strain of nonpathogenic Escherichia coli (K12).1 2 3

Uses for Lantus

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

Diabetes Mellitus

Treatment of adults and children ≥6 years of age with type 1 (previously called insulin-dependent) diabetes mellitus or adults with type 2 (previously called noninsulin-dependent) diabetes mellitus who require long-acting insulin for control of hyperglycemia.1 12 13

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Not the insulin of choice for treatment of diabetic ketoacidosis; short-acting IV insulins are preferred.1

Lantus Dosage and Administration

Administration

Administer by sub-Q injection.1 Should not be given IV.1

Sub-Q Administration

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

Administer once daily at the same time each day using a conventional insulin syringe.1

Rotate sites within an injection area so that no site is injected more than once every 1–2 weeks.1 6

Administer only if solution is clear and colorless with no particles visible.1 10 Syringe must not contain other drugs or residue.1 10

Dosage

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

Pediatric Patients

Diabetes Mellitus
Sub-Q

Individualize dosage.1

In children ≥6 years of age with type 1 diabetes mellitus, recommendations for changing from another insulin to insulin glargine are the same as for adults.1 3 (See Adults under Dosage.)

Adults

Diabetes Mellitus
Sub-Q

Individualize dosage.1

In a clinical study in patients with type 2 diabetes mellitus, the initial dosage of insulin glargine in insulin-naive patients receiving oral antidiabetic agents was 10 units once daily, with subsequent dosage adjustments based on blood glucose concentrations; total daily dosages ranged from 2–100 units.1

When patients were transferred from once-daily isophane insulin human or extended insulin human zinc to insulin glargine in clinical studies, the initial dosage generally was the same.1 3

When patients are transferred from twice-daily isophane insulin to insulin glargine once daily, the manufacturer recommends that the initial dosage be reduced by approximately 20% for the first week to reduce the risk of hypoglycemia;1 6 dosage should then be adjusted on the basis of blood glucose concentrations.1 5

Special Populations

Hepatic Impairment

Insulin glargine requirements may be reduced.1 Careful monitoring of blood glucose and adjustment of dosage may be necessary.1

Renal Impairment

Insulin glargine requirements may be reduced.1 Careful monitoring of blood glucose and adjustment of dosage may be necessary.1

Geriatric Patients

Conservative initial dosage, dose increments, and maintenance dosage recommended to avoid hypoglycemia.1

Cautions for Lantus

Contraindications

  • Known hypersensitivity to insulin glargine or any ingredient in the formulation.1

Warnings/Precautions

Warnings

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

Hypoglycemia

Most common adverse effect of insulins.1 2 4 5 Monitor blood glucose concentrations.1 2 4 5

Formulation Considerations

Make any change in insulin cautiously and only under medical supervision.1 5 Change in dosage may be required if insulin therapy is changed to insulin glargine.1

Adjustment of oral antidiabetic dosage may be necessary in patients receiving concomitant therapy with insulin glargine.1

Sensitivity Reactions

Hypersensitivity Reactions

Hypersensitivity reactions (e.g., skin reactions, angioedema, bronchospasm, hypotension, shock) reported rarely; may be life-threatening.1

General Precautions

Dermatologic Reactions

Atrophy or hypertrophy of sub-Q fat tissue may occur at sites of frequent insulin injections; injection site rotation may reduce or prevent these effects.1 5

Other local reactions (e.g., pain at injection site, redness, itching, hives, swelling, inflammation) also reported.1

Concurrent Illness

Insulin requirements may be altered during illness, emotional disturbances, or stress.1 4 5

Specific Populations

Pregnancy

Category C.1

Lactation

Insulin human is distributed into milk.1 Not known whether insulin glargine is distributed into milk; caution is advised if used in nursing women.1

Pediatric Use

Safety and efficacy not established in children <6 years of age.1

Common Adverse Effects

Hypoglycemia, injection site reactions, injection site pain, lipodystrophy, pruritus, rash, retinopathy.1

Interactions for Lantus

Many drugs affect glucose metabolism; if such drugs are used concomitantly, insulin glargine dosage adjustment and careful monitoring may be required.1

Specific Drugs1

Drugs That May Potentiate Hypoglycemic Effects

Alcohol

ACE inhibitors

Disopyramide

Fibrate derivatives

Fluoxetine

Guanethidine

MAO inhibitors

Oral antidiabetic agents

Propoxyphene

Salicylates

Somatostatin derivatives (e.g., octreotide)

Sulfa anti-infectives

Drugs That May Antagonize Hypoglycemic Effects

Calcium-channel blockers

Corticosteroids

Danazol

Diuretics

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

Isoniazid

Niacin

Phenothiazines

Somatropin

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

Thyroid hormones

Drugs That May Have a Variable Effect on Glycemic Control

Alcohol

β-Adrenergic blocking agents

Clonidine

Lithium salts

Pentamidine

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

β-Adrenergic blocking agents

Clonidine

Guanethidine

Reserpine

Lantus Pharmacokinetics

Absorption

Bioavailability

Following injection into sub-Q tissue, neutralization of insulin glargine solution results in formation of microprecipitates from which the drug is slowly released.1

Following sub-Q injection, absorption of insulin glargine is slower and more prolonged compared with that of isophane insulin human; serum concentration-time profile for insulin glargine is relatively constant over 24 hours.1

Onset

Following sub-Q injection, onset of hypoglycemic action is 1.1 hours.11 Substantial interindividual and intraindividual variation may occur based on tissue blood supply, temperature, exercise, and/or interindividual and intraindividual differences in response.1

Duration

Following sub-Q injection, duration of hypoglycemic action is 24 hours.1 Duration of action is similar following sub-Q injection at abdominal, deltoid, or thigh sites.1 Substantial interindividual and intraindividual variation in duration may occur based on tissue blood supply, temperature, exercise, and/or interindividual and intraindividual differences in response.1

Elimination

Metabolism

In the sub-Q tissue depot, insulin glargine is partially metabolized to form 2 metabolites with activity similar to that of insulin.1

Stability

Storage

Parenteral

Injection

With unopened vials and cartridges, 2–8°C.1 Do not freeze; discard if solution has been frozen.1

With opened vials, may keep unrefrigerated away from direct heat and light at temperature ≤30°C for up to 28 days if refrigeration is not possible;1 whether refrigerated or not, use vials within 28 days or discard.1

With cartridges in use in the OptiClick system, store at <30°C away from direct heat and light; do not refrigerate.1 Do not refrigerate the OptiClick system with or without the cartridge.1 Discard in-use cartridge system after 28 days.1

Compatibility

For information on systemic interactions resulting from concomitant use, see Interactions.

Parenteral

Must not mix with other insulins or dilute with other solutions;1 dilution or mixing may result in a cloudy solution and alter pharmacokinetic or pharmacodynamic profile of insulin glargine or mixed insulin in unpredictable manner.1

Actions

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

  • Pharmacologic effects comparable to those of insulin human;1 2 stimulates peripheral glucose uptake by tissues (e.g., skeletal muscle, fat), inhibits hepatic glucose production, inhibits lipolysis, inhibits proteolysis, and enhances protein synthesis.1 On molar basis, has approximately the same glucose-lowering effect as insulin human.1

Advice to Patients

  • Provide copy of manufacturer’s patient information.1 10

  • Importance of not mixing or diluting insulin glargine with any other insulins or solutions.1 Importance of using insulin glargine only if solution is clear and colorless with no particles visible.1

  • Importance of proper glucose monitoring, injection technique, and management of hyperglycemia or hypoglycemia.1 4 5 Risk of inadequate or variably timed food intake.1 Advise regarding insulin requirements in special situations such as intercurrent conditions (illness, stress, emotional disturbances), missed doses, or inadvertent administration of incorrect doses.1

  • Advise regarding product storage conditions.1

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs.1

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1 4

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

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Insulin Glargine

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

Injection, for subcutaneous use only

100 units/mL (U-100)

Lantus (with cresol; in vials and 3-mL cartridges for use in OptiClik)

Sanofi-Aventis

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 02/2014. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Lantus 100UNIT/ML Solution (SANOFI-AVENTIS U.S.): 10/$124.99 or 30/$348.97

Lantus SoloStar 100UNIT/ML Solution (SANOFI-AVENTIS U.S.): 15/$234.99 or 45/$661.95

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions August 1, 2009. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

References

1. Aventis Pharmaceuticals Inc. Lantus (insulin glargine [rDNA origin]) injection prescribing information. Kansas City, MO; 2005 Nov.

2. Gillies PS, Figgitt DP, Lamb HM. Insulin glargine. Drugs. 2000; 59:253-60. [PubMed 10730548]

3. Ratner RE, Hirsch IB, Neifing JL et al. Less hypoglycemia with insulin glargine in intensive insulin therapy for type 1 diabetes. Diabetes Care. 2000; 23:639-43. [IDIS 448667] [PubMed 10834423]

4. American Diabetes Association. Standards of medical care for patients with diabetes mellitus. Diabetes Care. 2000; 23(Suppl 1):S32.

5. American Diabetes Association. Insulin administration. Diabetes Care. 2000; 23(Suppl 1):S86.

6. Aventis Pharmaceuticals, Kansas City, MO: Personal communication.

7. Ratner RE, Hirsch IB, Mecca TE et al. Efficacy and safety of insulin glargine in subjects with type 1 diabetes: a 28-week randomized, NPH insulin-controlled trial. Diabetes. 1999; 48(Suppl 1):A120.

8. Rosenstock J, Schwartz S, Clark C et al. Efficacy and safety of HOE 901 (insulin glargine) in subjects with type 2 DM: a 28-week randomized, NPH insulin-controlled trial. Diabetes. 1999; 48(Suppl 1):A100.

9. Yki-Jarvinen H, Dressler A, Ziemen M et al. Comparison of insulin glargine (HOE901) vs NPH insulin during 1 year of insulin combination therapy in type 2 diabetes. Paper presented at the sixtieth Scientific Sessions of the American Diabetes Association. San Antonio, TX, 2000 June 9–13: Abstract No. 529. From website.

10. Aventis. Lantus (insulin glargine) injection patient information. Kansas City, MO; 2005 Mar.

11. AHFS drug information 2002. McEvoy GK, ed. Insulins general statement. Bethesda, MD: American Society of Health-System Pharmacists; 2003:2960-8.

12. Fritsche A, Schweitzer MA, Haring HU et al. Glimepiride combinated with morning insulin glargine, bedtime neutral protamine hagedorn insulin, or bedtime insulin glargine in patients with type 2 diabetes: a randomized controlled trial. Ann Intern Med. 2003; 138:952-9. [IDIS 499186] [PubMed 12809451]

13. Hamann A, Matthaei S, Rosak 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; 26:1738-44. [PubMed 12766103]

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