Tresiba Flexpen100IU/ml

Tresiba Flexpen is an ultra-long-acting basal insulin analog indicated for the following uses:

Established / FDA-approved uses

• To improve glycemic control in adults with type 1 diabetes mellitus, as part of a regimen that includes a separate rapid- or short-acting mealtime insulin.
• To improve glycemic control in adults with type 2 diabetes mellitus, either alone or in combination with oral antidiabetic agents and/or other insulins.
• To improve glycemic control in pediatric patients 1 year of age and older with type 1 diabetes mellitus.

Not indicated for

• Treatment of diabetic ketoacidosis (an intravenous, short-acting insulin is required in that setting).
• Type 2 diabetes in pediatric patients (safety and efficacy not established in this population).

Tresiba Flexpen is a basal (background) insulin only and must always be used together with a comprehensive diabetes management plan, including blood glucose monitoring and, where required, mealtime insulin.

Each mL of Insulin Degludec injection contains 100 units or 200 units of insulin degludec (a recombinant, ultra-long-acting human insulin analog) as the active ingredient, in a clear, colorless, neutral aqueous solution for subcutaneous injection.

Available as prefilled pen devices or vials, with excipients typically including glycerol, metacresol, phenol, zinc, and water for injection; a small amount of hydrochloric acid/sodium hydroxide may be added to adjust pH.

Tresiba Flexpen is a man-made (recombinant) analog of human insulin engineered for an ultra-long duration of action. Structurally, it differs from human insulin by deletion of the terminal amino acid threonine at position B30 and attachment of a glutamic acid linker and a C16 fatty diacid side chain to the lysine at position B29.

This modification allows Tresiba Flexpen to form stable, soluble multi-hexamer chains after subcutaneous injection, creating a slow-releasing depot under the skin. It is used as a once-daily basal insulin to help control blood glucose levels in people with type 1 or type 2 diabetes mellitus.

Tresiba Flexpen belongs to the therapeutic class of anti-diabetic agents (insulins), specifically the subclass of ultra-long-acting basal insulin analogs. It is used for the long-term background (basal) control of blood glucose in diabetes mellitus.

Mechanism

Insulin Degludec lowers blood glucose by binding to insulin receptors on muscle and fat cells, stimulating peripheral glucose uptake, and by inhibiting glucose output from the liver. It also inhibits lipolysis and proteolysis while enhancing protein synthesis.

Pharmacokinetics

• Absorption: After subcutaneous injection, Insulin Degludec forms soluble multi-hexamer depots from which monomers are slowly and continuously absorbed, giving a flat, predictable, and prolonged glucose-lowering profile with low day-to-day variability.
• Onset: Glucose-lowering effect begins within approximately 1 hour of injection.
• Duration: The glucose-lowering effect lasts beyond 42 hours in the therapeutic dose range.
• Half-life: Approximately 25 hours, largely independent of dose, and steady state is generally reached after 2–3 daily doses.
• Metabolism/Excretion: Degraded similarly to endogenous insulin, primarily via insulin-degrading enzyme; metabolites are inactive.

Tresiba Flexpen is given as a once-daily subcutaneous injection into the thigh, upper arm, or abdominal wall, with injection sites rotated to reduce the risk of lipodystrophy. It should never be administered intravenously or intramuscularly, and must not be mixed or diluted with other insulins or solutions. Patients should be trained in proper injection technique and self-monitoring of blood glucose.

Only well-established, clinically significant interactions with Tresiba Flexpen are listed below.

• Drugs that may increase hypoglycemic effect (raise hypoglycemia risk): other antidiabetic agents, ACE inhibitors, disopyramide, fibrates, fluoxetine, monoamine oxidase inhibitors (MAOIs), pentoxifylline, salicylates, and sulfonamide antibiotics.
• Drugs that may decrease hypoglycemic effect (raise blood glucose, reducing effectiveness): corticosteroids, danazol, diuretics, sympathomimetic agents, isoniazid, niacin, oral contraceptives/estrogens, phenothiazines, thyroid hormone replacement, and atypical antipsychotics.
• Beta-blockers, clonidine, and reserpine may blunt or mask the warning signs of hypoglycemia (such as tremor and palpitations), delaying recognition.
• Pramlintide or GLP-1 receptor agonists used together with Tresiba Flexpen have an additive glucose-lowering effect and increase hypoglycemia risk, often requiring a reduction in insulin dose.
• Alcohol can potentiate or prolong the hypoglycemic effect of Tresiba Flexpen.

The most common and most serious adverse reaction associated with Tresiba Flexpen is hypoglycemia (see Precautions and Warnings for full detail). Other reported side effects include:

• Injection site reactions (pain, redness, swelling, itching) and lipodystrophy (lipohypertrophy or lipoatrophy) with repeated injection at the same site.
• Weight gain.
• Peripheral edema (fluid retention), particularly when starting insulin therapy or intensifying glucose control.
• Hypokalemia (low blood potassium).
• Allergic reactions, which are usually mild (local rash, itching) but rarely can be severe, including generalized skin reactions, angioedema, bronchospasm, hypotension, or anaphylaxis.

Pregnancy

Insulin, including Tresiba Flexpen, does not cross the placenta in clinically relevant amounts, and insulin therapy is generally a preferred option for achieving glycemic control during pregnancy when medication is needed, including in pre-existing and gestational diabetes. However, Tresiba Flexpen should be used in pregnancy only if clearly needed, and potential benefit is judged by a physician to justify potential risk; insulin requirements often change during pregnancy and the postpartum period, so blood glucose should be monitored closely and dose adjusted under physician guidance.

Lactation

Insulin is expected to pass into breast milk in amounts similar to endogenous insulin and is not expected to have adverse effects on a breastfed infant; Tresiba Flexpen is commonly used in breastfeeding women who need insulin therapy. Nonetheless, use during breastfeeding should be under medical supervision, with attention to maternal dose and glucose monitoring.

• Hypoglycemia: The most common and most serious risk with Tresiba Flexpen; can be life-threatening if severe. Tresiba Flexpen has a flat, prolonged action profile associated with generally lower nocturnal hypoglycemia risk compared with some older basal insulins, but careful dose titration, consistent monitoring, and patient education on recognizing and treating hypoglycemia remain essential. Because of its long duration of action, hypoglycemia related to Tresiba Flexpen may take longer to resolve than with shorter-acting insulins.
• Not for diabetic ketoacidosis: Tresiba Flexpen must not be used to treat diabetic ketoacidosis; intravenous, rapid-acting/regular insulin is required in this setting.
• Injection site lipodystrophy: Repeated injection at the same site without rotation can cause lipodystrophy, which may alter insulin absorption; sites should be rotated with each injection.
• Hypokalemia: Tresiba Flexpen, like all insulins, can shift potassium into cells and cause hypokalemia, which may be serious (e.g., causing arrhythmia) if untreated; monitoring is advised in at-risk patients.
• Dose titration and monitoring: Any change in insulin regimen (type, brand, or dose) should be made cautiously and only under medical supervision, with careful blood glucose monitoring, especially during illness, changes in diet, exercise, or concomitant medication.
• Fluid retention with concomitant thiazolidinediones (TZDs): Using Tresiba Flexpen together with TZDs may increase the risk of fluid retention and heart failure, particularly in patients with pre-existing cardiac risk factors.
• Hypersensitivity reactions: Severe, generalized allergic reactions, including anaphylaxis, are rare but can be life-threatening; discontinue and seek medical care if suspected.
• Medication errors: Tresiba Flexpen is available in different pen strengths (e.g., U-100 and U-200); patients and caregivers must check the device and dose carefully before each injection to avoid dosing errors, and pens must never be shared between patients even with a new needle.

An excess dose of Tresiba Flexpen relative to food intake, physical activity, or energy expenditure can cause hypoglycemia, which may range from mild (sweating, shakiness, palpitations, hunger, confusion) to severe (seizure, loss of consciousness).

• Mild hypoglycemic episodes can usually be managed with oral glucose or a carbohydrate-containing snack or drink.
• Severe hypoglycemia with impaired consciousness may require assistance from another person and treatment with glucagon or intravenous glucose administered by a healthcare professional.
• Because Tresiba Flexpen has a prolonged, ultra-long duration of action, hypoglycemia following an overdose may develop or resolve slowly, and extended monitoring of blood glucose over many hours may be required.

Any suspected overdose or severe/prolonged hypoglycemia should be treated as a medical emergency — seek immediate medical attention or contact emergency services without delay.

Store unopened pens/vials of Tresiba Flexpen in a refrigerator (2°C to 8°C); do not freeze, and discard if it has been frozen. Once in use, the pen/vial may be kept at room temperature (below 30°C), away from direct heat and light, and must be discarded after 56 days even if some medicine remains. Keep out of reach of children.

• Renal impairment: Tresiba Flexpen can be used, but insulin requirements may be reduced due to decreased insulin clearance; blood glucose should be monitored closely and the dose individualized.
• Hepatic impairment: Insulin requirements may be altered due to reduced capacity for gluconeogenesis and insulin metabolism; closer glucose monitoring and dose adjustment are recommended.
• Elderly patients: Tresiba Flexpen can be used, but dose titration should be conservative, with close monitoring, as elderly patients may have reduced ability to recognize hypoglycemia symptoms and may have age-related decline in renal function.
• Pediatric patients: Safety and efficacy of Tresiba Flexpen are established in children 1 year of age and older with type 1 diabetes mellitus; safety and efficacy have not been established for type 2 diabetes in pediatric patients or for children under 1 year of age.

Tresiba Flexpen is used as a long-term, typically lifelong, basal insulin therapy for diabetes mellitus, continued for as long as needed to maintain glycemic control. Duration and dose should be reviewed periodically by the treating physician based on blood glucose control, HbA1c, and overall health status.

Antidiabetic agent; ultra-long-acting basal insulin analog.

Insulin Degludec acts by binding to insulin receptors, promoting glucose uptake by skeletal muscle and adipose tissue and suppressing hepatic glucose production. After subcutaneous injection, it self-associates into soluble, stable multi-hexamer chains that form a depot under the skin; individual Insulin Degludec monomers then separate slowly and continuously from this depot into the bloodstream, producing a flat, consistent, and prolonged (beyond 42 hours) glucose-lowering action with low day-to-day variability compared with older basal insulins.

Tresiba Flexpen is approved for use in pediatric patients 1 year of age and older with type 1 diabetes mellitus, with dosing individualized to the child's metabolic needs under specialist supervision and close blood glucose monitoring. Safety and efficacy of Tresiba Flexpen have not been established in children younger than 1 year of age or in pediatric patients with type 2 diabetes.