insulin detemir (Levemir, Levemir FlexTouch)

Dosing and uses of Levemir (insulin detemir)

• Adult
• Pediatric

 

Adult dosage forms and strengths

injectable solution

• 100 units/mL (10mL vial)

prefilled syringe

• 100 units/mL (3mL FlexTouch)

 

Type I or II Diabetes Mellitus

Once daily dosage: Administer SC with evening meal or at bedtime

Twice daily dosage: Administer SC with morning meal and either with evening meal, at bedtime, or 12 hr after the morning dose

Initial dose

• Type 1 diabetes: Approximately one third of the total daily insulin requirements SC; rapid-acting or short-acting, premeal insulin should be used to satisfy the remainder of the daily insulin requirements; 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 inadequately controlled on oral medication: 10 units/day SC (or 0.1-0.2 unit/kg/day) in evening or divided q12hr
• Type 2 diabetes inadequately controlled on GLP-1 receptor agonist: 10 units/day SC given once daily in evening
• Subsequently adjust dose based on blood glucose measurements

Conversion from other insulins

• If converting from insulin glargine: Change can be accomplished on a unit-to-unit basis
• If converting from NPH insulin: Change can be accomplished on a unit-to-unit basis; however, some patients with type 2 diabetes may require more insulin detemir than NPH insulin
• Closely monitor blood glucose during transition and in the initial weeks thereafter; concurrent rapid-acting or short-acting insulins or other concomitant antidiabetic treatment may require dose adjustment

 

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

Dose adjustments should be based on regular blood glucose testing

Adjust to achieve appropriate glucose controL

Dose adjustments

• Look for consistent pattern in blood sugars for >3 days
• Same time each day: Compare blood glucose level with previous levels that occurred at that time of day
• For each time of day: Calculate blood glucose range
• Calculate median blood glucose
• Consider eating and activity patterns during the day

Rate of dose adjustments

• Adjust only 1 insulin dose at a time
• Correct hypoglycemia first
• Correct highest blood sugars next
• If all blood sugars are high (within 2.75 mmol/L [50 mg/dL]): Correct morning fasting blood glucose first
• Change insulin doses in small increments: Type 1 diabetes (1-2 U change); type 2 diabetes (resistant to diet, exercise; 2-3 U change)

Sliding scales

• Many sliding scales exist to determine exact insulin dose based on frequent blood glucose monitoring
• Commonly written for q4hr blood glucose test
• Sliding scale coverage usually begins after blood glucose >11 mmol/L (200 mg/dL)
• If coverage is needed q4hr for 24 hr, then base insulin dose is adjusted first; sliding scale doses may be adjusted upwards as well

 

Pediatric dosage forms and strengths

injectable solution

• 100 units/mL (10mL vial)

prefilled syringe

• 100 units/mL (3mL FlexTouch)

 

Type 1 Diabetes Mellitus

<2 years: Safety and efficacy not established

≥2 years: Approximately one-third of the total daily insulin requirements SC; rapid-acting or short-acting, premeal insulin should be used to satisfy the remainder 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

Conversion from other insulins

• Change from basal insulin to insulin detemir can be done on a unit-to-unit basis (then adjust to achieve glycemic targets)
• Monitor closely during growth spurts and adjust dose accordingly

 

Levemir (insulin detemir) adverse (side) effects

Frequency not defined

Hypoglycemia

Headache

Influenza-like symptoms

Pallor

Palpitation

Tachycardia

Mental confusion

Redness

Urticaria

Weakness

Blurred vision

Itching

Hunger

Nausea

Lipodystrophy

Lipohypertrophy

Local allergic reaction

Hypokalemia

 

Warnings

Contraindications

Systemic allergic reactions

During episodes of hypoglycemia

 

Cautions

Never share pen between patients even if needle is changed

Long-acting insulin; do not use for circumstances that require rapid-acting insulin

Use with caution in patients with decreased insulin requirements, including those with diarrhea, nausea/vomiting, malabsorption, hypothyroidism, renal impairment, or hepatic impairment

Rapid changes in serum glucose may induce symptoms of hypoglycemia

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

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  

Use with caution in patients with increased insulin requirements, including those with fever, hyperthyroidism, trauma, or infection or who have undergone surgery

Pregnancy, lactation

Lower dose when used in combination with a GLP-1 receptor agonist to minimize the risk of hypoglycemia

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

 

Pregnancy and lactation

Pregnancy category: B; randomized, controlled trial (n=310) observed insulin detemir reduced Hgb A1C similarly to insulin NPH in pregnant women; no differences observed in fetuses and newborns

Lactation: Safe

 

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 Levemir (insulin detemir)

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: 60% SC; well absorbed

Onset: 3-4 hr

Peak onset: 6-8 hr (not pronounced; released at constant rate over 24 hr)

Duration: Up to 24 hr (range 5.7-23.2 hr)

 

Distribution

Protein bound: 98% bound to albumin

Vd: 0.1 L/kg

 

Elimination

Half-life elimination: 5-7 hr (dose dependent)

Excretion: Urine