insulin detemir

Insulin detemir is a type of insulin used to control blood sugar levels in adults and children above 2 years of age with type I diabetes mellitus and adults with type II diabetes. Insulin detemir is a biosynthetic product manufactured using DNA recombinant technology. Insulin detemir is a long-acting insulin administered once or twice daily to maintain basal levels of insulin other than at meal times when rapid-acting insulin is required to control the glucose surge. Insulin detemir is used in a regimen with rapid or short-action insulin in patients with diabetes type I.

Type I diabetes is a genetic autoimmune condition in which the immune cells destroy the insulin-producing cells in the pancreas, resulting in little or complete absence of insulin secretion. Type I diabetes develops typically in adolescence. Type II diabetes is more common and is mostly related to lifestyle, and develops later in life because the pancreas produces less insulin, or the body becomes resistant to insulin.

Insulin detemir is an insulin analog structurally similar to human insulin, a natural hormone produced by the pancreas. The pancreas releases insulin after a meal to regulate the metabolism of carbohydrates, fats and proteins absorbed from food. Diabetes is a metabolic disorder with high blood glucose levels (hyperglycemia), caused by insulin dysfunction which impairs the ability of cells to absorb glucose for energy. Diabetes affects the entire body and can damage all organs, particularly, nerves, kidneys and eyes.

Insulin detemir supplements the deficiency of natural insulin the body requires for regulating glucose metabolism and maintaining optimal glucose levels, and works similar to natural insulin. Insulin reduces blood glucose by stimulating the uptake of glucose from blood into the organs and tissues, particularly skeletal muscle, fat cells and the liver. Insulin also inhibits glucose production in the liver, inhibits breakdown of fats and proteins, and enhances protein synthesis. 

Insulin detemir is administered as a subcutaneous injection into the skin with a needle and syringe or a prefilled pen with metered doses. Insulin detemir takes effect in approximately 3 to 4 hours, and effects last up to a maximum of 24 hours. The long action of insulin detemir is from delayed systemic absorption from the subcutaneous tissue, and because it binds to albumin in blood which slows down its absorption. Insulin detemir should not be used to treat diabetic ketoacidosis, a serious complication of diabetes that requires emergency medical treatment.

• Do not administer insulin detemir to patients with hypersensitivity to any component of insulin detemir formulation.
  • Severe allergic reactions (anaphylaxis) have been reported following administration of insulin detemir.
  • If the patient develops hypersensitivity reactions, discontinue insulin detemir, treat appropriately and monitor until signs and symptoms resolve.
• Do not administer insulin detemir during episodes of low blood glucose (hypoglycemia).
• Train patients to self-administer insulin detemir injections with needles and syringes or prefilled pens, and advise them to never share their delivery devices with others, because sharing can lead to transmission of bloodborne infections.
• Repeated insulin injections into the same areas can cause changes in the fat tissue under the skin (lipodystrophy) or abnormal protein clumping in the skin (cutaneous amyloidosis). Injecting in these areas can reduce insulin absorption and result in hyperglycemia, and a sudden change in the injection site (to an unaffected area) may result in hypoglycemia. Advise patients to rotate injection sites regularly.
• Changes in insulin type, strength, manufacturer, or mode of administration can affect glycemic control and cause hyperglycemia or hypoglycemia. Insulin regimen changes should be made under close medical supervision with increased frequency of blood glucose monitoring. Patients with type II diabetes may require concomitant anti-diabetic treatment.
• Hypoglycemia is the most common adverse effect with all insulin therapies, including insulin detemir. Recovery from hypoglycemia may take longer with long-acting insulins than with short-acting insulins.
  • Risk of hypoglycemia is related to the insulin product’s duration of action and is highest at the time of its maximal effect.
  • Changes in meal patterns, physical activity and concomitant medications can increase the risk for hypoglycemia.
  • Impairment of liver or kidney function increases the risk for hypoglycemia.
  • Hypoglycemia can happen suddenly and symptoms differ in patients and may change over time in the same patient.
  • Patients with long-standing diabetes, diabetic nerve disease (neuropathy), recurrent hypoglycemia, or patients taking beta-blockers may have reduced awareness of hypoglycemic symptoms.
  • Hypoglycemia can affect concentration ability and reaction time and put the patient and others at risk when engaging in hazardous activities.
  • Severe hypoglycemia can cause seizure, loss of consciousness, temporary or permanent brain damage, and even death.
  • Monitor blood glucose more frequently in patients at high risk for hypoglycemia and patients who have reduced symptomatic awareness of hypoglycemia.
  • Educate patients and caregivers to self-monitor glucose levels, recognize and manage hypoglycemia appropriately.
• All insulins, including insulin detemir, cause a shift of potassium into the cells that can lead to low potassium (hypokalemia), which, if untreated, can cause respiratory paralysis and life-threatening irregular ventricular rhythm (ventricular arrhythmia) and death. Monitor potassium levels in patients at risk for hypokalemia, including patients taking potassium-lowering medications or medications sensitive to potassium concentrations.
• Concurrent use of insulin detemir with thiazolidinediones, a class of oral antidiabetic drugs known as peroxisome proliferator-activated receptor (PPAR)-gamma agonists, can cause dose-related fluid retention and increase the risk for heart failure. Closely monitor such patients for symptoms and if the patient develops heart failure, treat appropriately and consider discontinuation or dose reduction of PPAR-gamma agonist.

Common side effects of insulin detemir include:

• Hypoglycemia
• Upper respiratory tract infection
• Throat inflammation (pharyngitis)
• Bronchial inflammation (bronchitis)
• Nasal inflammation (rhinitis)
• Cough
• Headache
• Influenza-like illness
• Back pain
• Abdominal pain
• Gastroenteritis
• Nausea
• Vomiting
• Fever (pyrexia)
• Hypersensitivity reactions including:
  • Generalized allergy
  • Generalized skin reactions
  • Severe allergic reactions (anaphylaxis)
  • Swelling in subcutaneous and mucous tissue (angioedema)
  • Drop in blood pressure (hypotension)
  • Bronchospasm
  • Shock
• Transitory, reversible refraction disorder in the eye
• Transient worsening of diabetic retinopathy
• Acute painful peripheral neuropathy
• Injection site reactions including:
  • Pain
  • Redness (erythema)
  • Hives (urticaria)
  • Itching (pruritus)
  • Swelling (edema)
  • Inflammation
• Fat tissue changes (lipodystrophy) with long-term repeated injections including:
  • Wasting of skin tissue (lipoatrophy)
  • Thickening of skin tissue (lipohypertrophy)
• Weight gain
• Development of anti-insulin antibodies
• Swelling of extremities from fluid retention (peripheral edema)
• Localized cutaneous amyloidosis with repeated injections

Call your doctor immediately if you experience any of the following symptoms or serious side effects while using this drug:

• Serious heart symptoms include fast or pounding heartbeats, fluttering in your chest, shortness of breath, and sudden dizziness;
• Severe headache, confusion, slurred speech, severe weakness, vomiting, loss of coordination, feeling unsteady;
• Severe nervous system reaction with very stiff muscles, high fever, sweating, confusion, fast or uneven heartbeats, tremors, and feeling like you might pass out; or
• Serious eye symptoms include blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights.

This is not a complete list of all side effects or adverse reactions that may occur from the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may also report side effects or health problems to the FDA at 1-800-FDA-1088.

Injectable solution

• 100 units/mL (10mL vial)

Prefilled syringe

• 100 units/mL (3mL FlexTouch)

Adult:

Type I or II Diabetes Mellitus

• Once daily dosage: Administer subcutaneously (SC) with evening meal or at bedtime
• Twice daily dosage: Administer SC with morning meal and either with evening meal, at bedtime, or 12 hours after the morning dose

Initial dose

• Type 1 diabetes
  • Approximately one third of total daily insulin requirements SC
  • Use rapid-acting or short-acting, premeal insulin to satisfy remainder of 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 once every 12 hours
  • 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

• Converting from insulin glargine: Change can be accomplished on a unit-to-unit basis
• Converting from NPH insulin: Unit-to-unit basis possible; 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 longer than 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 once every 4 hours blood glucose test
• Sliding scale coverage usually begins after blood glucose is above 11 mmol/L (200 mg/dL)
• If coverage is needed once every 4 hours for 24 hours, then base insulin dose is adjusted first; sliding scale doses may be adjusted upwards as well

Pediatric:

Type 1 Diabetes Mellitus

Children below 2 years

• Safety and efficacy not established

Children 2 years and above

• Approximately one-third of the total daily insulin requirements SC
• Rapid-acting or short-acting, premeal insulin should be used to satisfy remainder of daily insulin requirements
• Usual daily maintenance range in adolescents is 1.2 units/kg/day or less during growth spurts

Dosing Considerations

• Dosage of human insulin, which is always expressed in USP units, must be based on 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

Overdose

• Overdose of insulin detemir relative to food intake, energy expenditure or both can lead to severe hypoglycemia and hypokalemia.
• Mild hypoglycemia can be treated with oral glucose and appropriate adjustments in drug dosage, meal patterns and exercise, as required.
• Treatment of severe hypoglycemic episodes with coma, seizure or neurologic impairment may require concentrated intravenous glucose or intramuscular or subcutaneous injection of glucagon. In addition, sustained carbohydrate intake and monitoring of the patient may be required to prevent recurrence of hypoglycemia.
• Hypokalemia should be corrected with potassium supplementation.

Inform your doctor of all medications you are currently taking, who can advise you on any possible drug interactions. Never begin taking, suddenly discontinue, or change the dosage of any medication without your doctor’s recommendation.

• Severe interactions of insulin detemir include:
  • pramlintide
• Serious interactions of insulin detemir include:
  • ethanol
  • macimorelin
• Insulin detemir has moderate interactions with at least 130 different drugs.
• Insulin detemir has mild interactions with at least 77 different drugs.

The drug interactions listed above are not all of the possible interactions or adverse effects. For more information on drug interactions, visit the RxList Drug Interaction Checker.

It is important to always tell your doctor, pharmacist, or health care provider of all prescription and over-the-counter medications you use, as well as the dosage for each, and keep a list of the information. Check with your doctor or health care provider if you have any questions about the medication.

• Available data on the use of insulin detemir in pregnant women have not identified a drug-associated risk of major birth defects, miscarriage or other adverse maternal or fetal outcomes.
• The risk for major birth defects is higher in pregnant women with pre-gestational diabetes, who are likely to have more frequent hyperglycemic and hypoglycemic episodes during pregnancy. Good glycemic control before conception and throughout pregnancy is essential for maternal and fetal health.
• Poorly controlled diabetes in pregnancy increases the maternal risk for diabetic ketoacidosis, preeclampsia, spontaneous abortions, preterm delivery, stillbirth and delivery complications, and fetal risks for birth defects and abnormally large growth (macrosomia).
• Available data show that human insulin products, including insulin detemir are excreted in breastmilk. There are no reports of adverse effects on the breastfed infant from exposure to insulin products in breastmilk. There is no information on the effects of insulin products on milk production.
• Decision to breastfeed during treatment with insulin detemir should be based on the mother’s clinical need for the drug, the developmental and health benefits of breastfeeding and potential risks to the breastfed infant from exposure to the drug or mother’s underlying condition.

• Never share your pen, needles, or syringes with others, or use those used by others.
• Always check labels before every injection to avoid errors of mix-up with other insulin products.
• Do not transfer insulin detemir from the pen into a syringe, the syringe markings will not be a correct measure and can result in overdose and hypoglycemia.
• Administer your insulin detemir injections exactly as prescribed, any regimen change must be done only under your physician’s supervision.
• Rotate your injection sites and do not inject into areas of skin that have scars, pits, lumps, scales, or are tender or bruised.
• Learn to monitor glucose levels and to recognize symptoms of hypoglycemia. Always carry sweets such as hard candy for immediate use and seek medical help if symptoms don’t resolve.
• Report to your physician immediately if you experience any allergic reaction to insulin detemir.
• Avoid alcohol, it can have an additive effect and increase the risk for hypoglycemia.
• Hypoglycemia can impair concentration ability and reaction time, be cautious about activities such as driving and operating heavy machinery.
• Store your insulin detemir delivery devices safely out of reach of children.
• In case of overdose, seek medical help immediately or call Poison Control.