Detemir

Uses

Detemir is a long-acting human insulin analog used to improve glycemic control in adults and children with diabetes mellitus.

Important Limitations of Use: Not recommended for treating diabetic ketoacidosis. Use intravenous, rapid acting or short-acting insulin instead.

Detemir is also used to associated treatment for these conditions: Type 1 Diabetes Mellitus, Type 2 Diabetes Mellitus

How Detemir works

Insulin detemir binds to the insulin receptor (IR), a heterotetrameric protein consisting of two extracellular alpha units and two transmembrane beta units. The binding of insulin to the alpha subunit of IR stimulates the tyrosine kinase activity intrinsic to the beta subunit of the receptor. The bound receptor autophosphorylates and phosphorylates numerous intracellular substrates such as insulin receptor substrates (IRS) proteins, Cbl, APS, Shc and Gab 1. Activation of these proteins leads to the activation of downstream signalling molecules including PI3 kinase and Akt. Akt regulates the activity of glucose transporter 4 (GLUT4) and protein kinase C (PKC), both of which play critical roles in metabolism and catabolism. Insulin detemir’s long duration of action appears to be a result of slow systemic absorption from the injection site and delayed distribution to target tissues. The myristic acid side chain on insulin detemir increases self-association and gives it a high binding affinity to serum albumin. These features slow its distribution into target tissues and prolong its duration of action.

Dosage

Detemir dosage

Adult: In insulin-naive patients with type 2 DM who are not well controlled on oral antidiabetic drugs: Initial: 0.1 -0.2 unit/kg once daily in the evening or 10 unit 1-2 times/day, adjust subsequently based on glycaemic control.

In patients on basal insulin only: May substitute with insulin detemir on a unit-for-unit basis based on the current basal insulin dosage, adjust subsequently to achieve glycaemic targets.

Side Effects

Hypoglycaemia, lipodystrophy, pruritus, rash, wt gain, sodium retention and oedema. Inj site reactions e.g. pain, itching, hives, swelling and inflammation. Influenza-like symptoms, Pallor, Palpitation, Tachycardia, Mental confusion, Weakness, Blurred vision, Itching, Hunger, Nausea.

Toxicity

Hypoglycemia may occur with inappropriately high doses. Neurogenic (autonomic) signs and symptoms of hypoglycemia include trembling, palpitations, sweating, anxiety, hunger, nausea and tingling. Neuroglycopenic signs and symptoms of hypoglycemia include difficulty concentrating, lethargy/weakness, confusion, drowsiness, vision changes, difficulty speaking, headache, and dizziness. Mild hypoglycemia is characterized by the presence of autonomic symptoms. Moderate hypoglycemia is characterized by the presence of autonomic and neuroglycopenic symptoms. Individuals may become unconscious in severe cases of hypoglycemia. Injection site reactions may also occur. Symptoms include: redness, inflammation, bruising, swelling and itching at the injection site.

Precaution

Renal or hepatic impairment. Regular monitoring of blood glucose and HbA1c. Continuous rotation of the inj site within a given area to reduce inj site reactions. Pregnancy, lactation

Interaction

Possible absence of hypoglycaemic warning symptoms with beta-blockers. Increased blood sugar with thiazide diuretics, corticosteriods, chlorpromazine, tibolone, isoniazid, niacin, some calcium-channel blockers such as diltiazem or nifedipine, diazoxide, lithium and thyroid hormones. Increased risk of hypoglycemia with disopyramide, larges doses of aspirin, gatifloxacin, MAOIs, mebanazine, nandrolone, pegvisomant, testosterone. Decreased insulin resistance with octreotide and lanreotide. Increased risk of wt gain and peripheral oedema with pioglitazone, rosiglitazone. Decreased effect of sermorelin.

Food Interaction

• Take with food. Once daily administration should be given with the evening meal or prior to bedtime.

Volume of Distribution

Insulin detemir has an apparent volume of distribution of approximately 0.1 L/kg.

Elimination Route

Maximum serum concentrations are reached 6 to 8 hours following subcutaneous injection. The duration of action of insulin detemir is mediated by slowed systemic absorption of insulin detemir molecules from the injection site due to self-association of the drug molecule. When single dose of 0.5 units/kg of insulin detemir was given to adult type 1 diabetes patients, the maximum serum concentration (Cmax) was 4,641 ± 2,299 pmol/L. Insulin detemir has a slow and prolonged absorption and a relatively constant concentration/time profile over 24 hours with no pronounced peak. The median time to maximum serum insulin concentration was 12 hours after injection. On average, serum insulin concentrations declined to baseline by approximately 24 hours. The absolute bioavailability of insulin detemir is approximately 60%.

Half Life

After subcutaneous administration in patients with type 1 diabetes, insulin detemir has a terminal half-life of 5 to 7 hours depending on dose.

Clearance

Apparent clearance (CL/F), type 1 diabetes adult patients = 3.41 ± 1.00 L/min·kg

Pregnancy & Breastfeeding use

Pregnancy Category B. Animal reproduction studies have failed to demonstrate a risk to the fetus and there are no adequate and well-controlled studies in pregnant women OR Animal studies have shown an adverse effect, but adequate and well-controlled studies in pregnant women have failed to demonstrate a risk to the fetus in any trimester.

Nursing Mothers: It is unknown whether Insulin detemir is excreted in human milk. Because many drugs, including human insulin, are excreted in human milk, use caution when administering Insulin detemir to a nursing woman. Women with diabetes who are lactating may require adjustments of their insulin doses.

Contraindication

Detemir is contraindicated in patients with hypersensitivity to Detemir or any of its excipients. Reactions have included anaphylaxis

Special Warning

Pediatric Use: The pharmacokinetics, safety and effectiveness of subcutaneous injections of Detemir have been established in pediatric patients (age 6 to 17 years) with type 1 diabetes. Detemir has not been studied in pediatric patients younger than 6 years of age with type 1 diabetes. Detemir has not been studied in pediatric patients with type 2 diabetes. The dose recommendation when converting to Detemir is the same as that described for adults. As in adults, the dosage of Detemir must be individualized in pediatric patients based on metabolic needs and frequent monitoring of blood glucose.

Geriatric Use: In controlled clinical trials comparing Detemir to NPH insulin or insulin glargine, 64 of 1624 patients (3.9%) in the type 1 diabetes trials and 309 of 1082 patients (28.6%) in the type 2 diabetes trials were≥65 years of age. A total of 52 (7 type 1 and 45 type 2) patients (1.9%) were ≥75 years of age. Nooverall differences in safety or effectiveness were observed between these patients and younger patients, but small sample sizes, particularly for patients ≥65 years of age in the type 1 diabetes trials and for patients ≥75 years of age in all trials limits conclusions. Greater sensitivity of some older individuals cannot be ruled out. In elderly patients with diabetes, the initial dosing, dose increments, and maintenance dosage should be conservative to avoid hypoglycemia. Hypoglycemia may be difficult to recognize in the elderly.

Acute Overdose

An excess of insulin relative to food intake, energy expenditure, or both may lead to severe and sometimes prolonged and life-threatening hypoglycemia. Mild episodes of hypoglycemia usually can be treated with oral glucose. Adjustments in drug dosage, meal patterns, or exercise may be needed. More severe episodes with coma, seizure, or neurologic impairment may be treated with intramuscular/subcutaneous glucagon or concentrated intravenous glucose. After apparent clinical recovery from hypoglycemia, continued observation and additional carbohydrate intake may be necessary to avoid recurrence of hypoglycemia

Storage Condition

Unused (unopened) Detemir should be stored in the refrigerator between 2° and 8°C. Do not store in the freezer or directly adjacent to the refrigerator cooling element. Do not freeze. Do not use Detemir if it has been frozen. Unused (unopened) Detemir can be kept until the expiration date printed on the label if it is stored in a refrigerator. Keep unused Detemir in the carton so that it stays clean and protected from light.

If refrigeration is not possible, unused (unopened) Detemir can be kept unrefrigerated at room temperature, below 30°C as long as it is kept as cool as possible and away from direct heat and light. Unrefrigerated Detemir should be discarded 42 days after it is first kept out of the refrigerator, even if the FlexPen or vial still contains insulin.

Innovators Monograph

You find simplified version here Detemir