insulin glargine (Lantus, Lantus SoloStar, Toujeo, Basaglar)

Dosing and uses of Lantus, Toujeo (insulin glargine)

• Adult
• Pediatric

 

Adult dosage forms and strengths

injectable solution

• 100 units/mL (Lantus; 10mL vial)
• 100 units/mL (Lantus SoloSTAR; Basaglar KwikPen; 3 mL disposable prefilled pens)
• 300 units/mL (Toujeo; 1.5 mL SolosStar disposable prefilled pen)
• Note: Toujeo designed to release the insulin more gradually; thus, the product has been labeled an ultralong-acting insulin

 

Type 1 or 2 Diabetes Mellitus

Lantus (long-acting) and Toujeo (ultra long-acting) are recombinant human insulin analogues indicated to improve glycemic control in adults with type 1 or 2 diabetes mellitus

 

Dosing Considerations

Indicated for once-daily SC administration; exhibits relatively constant glucose-lowering profile over 24 hr

May be administered at any time during the day; should be administered SC once daily at the same time every day

Dose must be individualized based on clinical response; blood glucose monitoring is essential in all patients receiving insulin therapy

Patients adjusting the amount or timing of dosage should do so only under medical supervision with appropriate glucose monitoring

In patients with type 1 diabetes, insulin glargine must be used in regimens with short-acting insulin

Should not be administered IV or via an insulin pump; IV administration of the usual SC dose could result in severe hypoglycemia

As with all insulins, injection sites should be rotated within the same region (abdomen, thigh, or deltoid) from one injection to the next to reduce the risk of lipodystrophy; no clinically relevant difference in insulin glargine absorption after abdominal, deltoid, or thigh SC administration

As with all insulins, the rate of absorption and, consequently, the onset and duration of action may be affected by exercise and other variables (eg, stress, intercurrent illness, changes in coadministered drugs, meal patterns)

Initial dose

• Type 1 diabetes mellitus: Starting dose should be approximately one third of the total daily insulin requirements; short-acting, premeal insulin should be used to satisfy the remaining two thirds of the daily insulin requirements; insulin glargine should be used in combination with a short-acting or rapid-acting insulin; usual daily maintenance range is 0.5-1 unit/kg/day in divided doses; nonobese may require 0.4-0.6 unit/kg/day; obese may require 0.6-1.2 units/kg/day
• Type 2 diabetes mellitus: Starting dose in patients who are not currently treated with insulin is 10 units (or 0.2 unit/kg) once daily
• Dosage should be individualized under the supervision of a healthcare provider in accordance with the needs of the patient and adjusted according to blood glucose measuremen

Converting from other insulins

• If changing from a treatment regimen with an intermediate- or long-acting insulin to a regimen with insulin glargine, the amount and timing of shorter-acting insulins and doses of any oral antidiabetic drugs may need to be adjusted
• From once-daily NPH insulin to once-daily insulin glargine: Initial dose is the same as the dose of NPH that is being discontinued
• From twice-daily NPH insulin to once-daily insulin glargine: Initial dose is 80% of the total daily NPH dose that is being discontinued; this dose reduction will lower the likelihood of hypoglycemia
• Switching from intermediate-to-long acting insulins to Toujeo
  • To minimize the risk of hypoglycemia when changing patients from a once daily long-acting or intermediate-acting insulin product to Toujeo, the starting dose of Toujeo can be the same as the once daily long-acting dose
  • For patients controlled on Lantus (insulin glargine, 100 units/mL) expect that a higher daily dose of Toujeo will be needed to maintain the same level of glycemic control
• Switching from intermediate-to-long-acting insulins to Lantus
  • If changing from a treatment regimen with an intermediate- or long-acting insulin to Lantus, a change in the dose of the basal insulin may be required and the amount and timing of the shorter-acting insulins and doses of any oral antidiabetic drugs may be needed to be adjusted
  • If changing patients from once daily Toujeo to once daily Lantus, the recommended initial Lantus dose is 80% of the Toujeo dose that is being discontinued; this dose reduction will lower the likelihood of hypoglycemia

 

Limitation of Use

Not recommended for treating diabetic ketoacidosis

 

Pediatric dosage forms and strengths

injectable solution

• 100 units/mL (Lantus; 10mL vial)
• 100 units/mL (Lantus SoloSTAR; Basalglar KwikPen; 3 mL disposable prefilled pens)

 

Type 1 Diabetes Mellitus

Lantus is a long-acting human insulin analogue indicated to improve glycemic control in children with type 1 diabetes mellitus; Toujeo is not approved for use in children

<6 years: Safety and efficacy not established

≥6 years: Approximately one third of the total daily insulin requirements SC; rapid-acting or short-acting, premeal insulin should be used to satisfy the remaining two thirds of the daily insulin requirements; usual daily maintenance range in adolescents is ≤1.2 units/kg/day during growth spurts

Dosing considerations

• Dosage of human insulin, which is always expressed in USP units, must be based on the results of blood and urine glucose tests and must be carefully individualized to optimal effect
• If changing from a treatment regimen with an intermediate- or a long-acting insulin to a regimen with insulin glargine, the amount and timing of shorter-acting insulins and doses of any oral antidiabetic drugs may need to be adjusted
• If changing from once-daily NPH insulin to once-daily insulin glargine: Initial dose is the same as the dose of NPH that is being discontinued
• If changing from twice-daily NPH insulin to once-daily insulin glargine: Initial dose is 80% of the total daily NPH dose that is being discontinued; this dose reduction will lower the likelihood of hypoglycemia

 

Lantus, Toujeo (insulin glargine) adverse (side) effects

Frequency not defined

Headache

Influenza-like symptoms

Dyspepsia

Diarrhea

Back pain

Pharyngitis

Lipodystrophy

Lipohypertrophy

Pallor

Palpitation

Tachycardia

Local allergic reaction

Hypokalemia

Peripheral edema

 

Warnings

Contraindications

Documented hypersensitivity

During episodes of hypoglycemia

 

Cautions

Toujeo and Lantus are not interchangeable

Not recommended for treating diabetic ketoacidosis; use IV short-acting insulin instead

Do not administer IV or via an insulin pump

Do not dilute or mix with other insulin or solution

Never share insulin pens between patients, even if the needle is changed

Decreased insulin requirements: Diarrhea, nausea/vomiting, malabsorption, hypothyroidism, renal impairment, hepatic impairment

Increased insulin requirements include fever, hyperthyroidism, trauma, infection, surgery

Hyper-or hypoglycemia may occur with changes in insulin regimen; carry out under close medical supervision

Increase frequency of glucose monitoring with changes to insulin dosage, co-administered glucose lowering medications, meal pattern, physical activity; and in patients with renal or hepatic impairment and hypoglycemia unawareness

Accidental mix-ups between insulin products can occur; instruct patients to check insulin labels before injection

Rapid changes in serum glucose may induce symptoms of hypoglycemia

Hypoglycemia is the most common cause of adverse reactions (eg, headache, tachycardia)

May cause a shift in potassium from extracellular to intracellular space, possibly leading to hypokalemia; caution when coadministered with potassium-lowering drugs or conditions that may decrease potassium

Frequent glucose monitoring and insulin dose reduction may be required with renal or hepatic impairment; not recommended during periods of rapidly declining renal or hepatic function because of risk for prolonged hypoglycemia

Use cautioin during pregnancy

Thiazolidinediones are peroxisome proliferator-activated receptor (PPAR)-gamma agonists and can cause dose-related fluid retention, particularly when used in combination with insulin; fluid retention may lead to or exacerbate heart failure; monitor for signs and symptoms of heart failure, treat accordingly, and consider discontinuing thiazolidinediones

Cancer risk data inconclusive

• The FDA reviewed 4 published observational studies, 3 of which suggested an increased risk of cancer associated with insulin glargine
• It was determined that the evidence presented in these studies is inconclusive due to methodologic limitations
• The duration of patient follow-up in all 4 studies was shorter than that which is generally considered necessary to evaluate cancer risk from drug exposure
• Also, the 4 studies provided limited information on patients' use of insulin products; some studies did not take into account whether the patients used any antidiabetic drugs before the study time period or whether there were any changes in how patients used these drugs during the study period
• Furthermore, risk factors for cancer (eg, smoking, family history of cancer, obesity) may not have been adequately controlled for in these studies

 

Pregnancy and lactation

Pregnancy category: C

Lactation: Considered safe for use while breast feeding

 

Pregnancy categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

 

Pharmacology of Lantus, Toujeo (insulin glargine)

Mechanism of action

Regulates glucose metabolism

Insulin and its analogues lower blood glucose by stimulating peripheral glucose uptake, especially by skeletal muscle and fat, and by inhibiting hepatic glucose production; insulin inhibits lipolysis and proteolysis and enhances protein synthesis; targets include skeletal muscle, liver, and adipose tissue

 

Absorption

Bioavailability: Delayed absorption from SC site

Onset of action: 3-4 hr

Duration: 24 hr (range: 10.8 hr to >24 hr)

Peak plasma time: Forms microprecipitate in fatty tissue from which a small amount of insulin is gradually released; no pronounced peaks; released at constant rate over >24 h

 

Metabolism

Adipose tissue/muscle

Partly metabolized at the carboxyl terminus of the B chain in the subcutaneous depot to form 2 active metabolites with in vitro activity similar to that of insulin

Metabolites (active): M1 (21A-Gly-insulin) and M2 (21A-Gly-des-30BThr-insulin)

 

Elimination

Excretion: Urine

 

Administration

Instructions

Inject SC once daily into the abdominal area, thigh, or deltoid at the same time each day

Rotate injection sites within the same region from 1 injection to the next to reduce the risk of lipodystrophy

Individualize and titrate dose based on the individual’s metabolic needs, blood glucose monitoring results, and glycemic control goaL

The dosage ranges from 1 to 80 units per each injection

To minimize the risk of hypoglycemia titrate the dose no more frequently than every 3-4 day

Dosage adjustments may be needed with changes in physical activity, changes in meal patterns (ie, macronutrient content or timing of food intake), changes in renal or hepatic function, or during acute illness to minimize the risk of hypoglycemia or hyperglycemia

To minimize the risk of hypoglycemia, do not administer IV, IM, or via insulin pump

To minimize the risk of hypoglycemia, do not dilute or mix with any other insulin products or solutions

 

Storage

Unopened vial or pen (not in-use)

• Refrigerated (36-46°F [2-8°C]): Until expiration date
• Unrefrigerated and kept from direct heat and light (ie, temperature does not exceed 86°F [30°C]): Up to 28 days
• Do not freeze

Opened vial or pen (in-use)

• Vial: 28 days at room temperature or refrigerated
• Pen: 28 days; store only at room temperature (do not refrigerate)