TRESIBA- insulin degludec injection, solution
Novo Nordisk
1 INDICATIONS AND USAGE
TRESIBA is indicated to improve glycemic control in patients 1 year of age and older with diabetes mellitus.
Limitations of Use
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Not recommended for the treatment of diabetic ketoacidosis
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Not recommended for pediatric patients requiring less than 5 units of TRESIBA
2 DOSAGE AND ADMINISTRATION
2.1 Important Administration Instructions
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Always check insulin labels before administration [see Warnings and Precautions (5.4)].
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Inspect visually for particulate matter and discoloration. Only use TRESIBA if the solution appears clear and colorless.
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Train patients on proper use and injection technique before initiating TRESIBA. Training reduces the risk of administration errors such as needle sticks and incomplete dosing.
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Inject TRESIBA subcutaneously into the thigh, upper arm, or abdomen.
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Rotate injection sites within the same region from one injection to the next to reduce the risk of lipodystrophy [see Adverse Reactions (6.1)].
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DO NOT administer TRESIBA intravenously, intramuscularly or in an insulin infusion pump.
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DO NOT dilute or mix TRESIBA with any other insulin products or solutions.
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DO NOT transfer TRESIBA from the TRESIBA pen into a syringe for administration [see Warnings and Precautions (5.4)].
2.2 General Dosing Instructions
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In adults, inject TRESIBA subcutaneously once-daily at any time of day.
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In pediatric patients inject TRESIBA subcutaneously once-daily at the same time every day.
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Individualize and titrate the dose of TRESIBA based on the patient's metabolic needs, blood glucose monitoring results, and glycemic control goal.
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The recommended days between dose increases is 3 to 4 days.
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Dose adjustments may be needed with changes in physical activity, changes in meal patterns (i.e., 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 [see Warnings and Precautions (5.3)].
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For adult patients, instruct patients who miss a dose of TRESIBA to inject their daily dose during waking hours upon discovering the missed dose. Instruct patients to ensure that at least 8 hours have elapsed between consecutive TRESIBA injections.
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For pediatric patients, instruct patients who miss a dose of TRESIBA to contact their healthcare provider for guidance and to monitor blood glucose levels more frequently until the next scheduled TRESIBA dose.
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DO NOT perform dose conversion when using the TRESIBA U-100 or U-200 FlexTouch pens. The dose window for both the TRESIBA U-100 and U-200 FlexTouch pens shows the number of insulin units to be delivered and NO conversion is needed.
2.3 Starting Dose in Insulin Na�ve Patients
Type 1 Diabetes Mellitus:
The recommended starting dose of TRESIBA in insulin na�ve patients with type 1 diabetes is approximately one-third to one-half of the total daily insulin dose. The remainder of the total daily insulin dose should be administered as a short-acting insulin and divided between each daily meal. As a general rule, 0.2 to 0.4 units of insulin per kilogram of body weight can be used to calculate the initial total daily insulin dose in insulin na�ve patients with type 1 diabetes.
Type 2 Diabetes Mellitus:
The recommended starting dose of TRESIBA in insulin na�ve patients with type 2 diabetes mellitus is 10 units once daily.
2.4 Starting Dose in Patients Already on Insulin Therapy
Adults with Type 1 or Type 2 Diabetes Mellitus:
Start TRESIBA at the same unit dose as the total daily long or intermediate-acting insulin unit dose.
Pediatric Patients 1 Year of Age and Older with Type 1 or Type 2 Diabetes Mellitus:
Start TRESIBA at 80% of the total daily long or intermediate-acting insulin unit dose to minimize the risk of hypoglycemia [see Warnings and Precautions (5.2)].
3 DOSAGE FORMS AND STRENGTHS
TRESIBA is available as a clear, and colorless solution for injection in:
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100 units/mL (U-100): 3 mL FlexTouch disposable prefilled pen
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200 units/mL (U-200): 3 mL FlexTouch disposable prefilled pen
4 CONTRAINDICATIONS
TRESIBA is contraindicated:
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During episodes of hypoglycemia [see Warnings and Precautions (5.3)].
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In patients with hypersensitivity to TRESIBA or one of its excipients
ADVERSE REACTIONS
The following adverse reactions are also discussed elsewhere:
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Hypoglycemia [see Warnings and Precautions (5.3)]
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Hypersensitivity and allergic reactions [see Warnings and Precautions (5.5)]
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Hypokalemia [see Warnings and Precautions (5.6)]
DESCRIPTION
TRESIBA (insulin degludec injection) is a long-acting basal human insulin analog for subcutaneous injection. Insulin degludec is produced by a process that includes expression of recombinant DNA in Saccharomyces cerevisiae followed by chemical modification.
Insulin degludec differs from human insulin in that the amino acid threonine in position B30 has been omitted and a side-chain consisting of glutamic acid and a C16 fatty acid has been attached (chemical name: LysB29(Nε-hexadecandioyl-γ-Glu) des(B30) human insulin). Insulin degludec has a molecular formula of C274 H411 N65 O81 S6 and a molecular weight of 6103.97
TRESIBA is a sterile, aqueous, clear, and colorless solution that contains insulin degludec 100 units/mL (U-100) or 200 units/mL (U-200).
Inactive ingredients for the 100 units/mL are: glycerol 19.6 mg/mL, phenol 1.50 mg/mL, metacresol 1.72 mg/mL, zinc 32.7 mcg/mL and water for injection.
Inactive ingredients for the 200 units/mL are glycerol 19.6 mg/mL, phenol 1.50 mg/mL, metacresol 1.72 mg/mL, zinc 71.9 mcg/mL and water for injection.
TRESIBA has a pH of approximately 7.6. Hydrochloric acid or sodium hydroxide may be added to adjust pH.
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
The primary activity of insulin, including TRESIBA, is regulation of glucose metabolism. Insulin and its analogs lower blood glucose by stimulating peripheral glucose uptake, especially by skeletal muscle and fat, and by inhibiting hepatic glucose production. Insulin also inhibits lipolysis and proteolysis, and enhances protein synthesis. TRESIBA forms multi-hexamers when injected into the subcutaneous tissue resulting in a subcutaneous insulin degludec depot. The protracted time action profile of TRESIBA is predominantly due to delayed absorption of insulin degludec from the subcutaneous tissue to the systemic circulation and to a lesser extent due to binding of insulin-degludec to circulating albumin.
PATIENT COUNSELING INFORMATION
Advise the patient and/or caregiver to read the FDA-approved patient labeling (Patient Information and Instructions for Use)
Never Share a TRESIBA FlexTouch Pen Between Patients
Advise patients that they should never share a TRESIBA FlexTouch, pen device with another person, even if the needle is changed, because doing so carries a risk for transmission of blood-borne pathogens [see Warnings and Precautions (5.1)].
Hyperglycemia or Hypoglycemia
Inform patients that hypoglycemia is the most common adverse reaction with insulin. Inform patients of the symptoms of hypoglycemia. Inform patients that the ability to concentrate and react may be impaired as a result of hypoglycemia. This may present a risk in situations where these abilities are especially important, such as driving or operating other machinery. Advise patients who have frequent hypoglycemia or reduced or absent warning signs of hypoglycemia to use caution when driving or operating machinery.
Advise patients that changes in insulin regimen can predispose to hyper- or hypoglycemia.
Advise patients that changes in insulin regimen should be made under close medical supervision [see Warnings and Precautions (5.2)].
Medication Errors
Inform patients to always check the insulin label before each injection [see Warnings and Precautions (5.4)]. TRESIBA FlexTouch pen is available in concentrations of 100 units/mL or 200 units/mL.
Inform patients that the dose counter of TRESIBA FlexTouch pen shows the number of units of TRESIBA to be injected. NO dose re-calculation is required [see Dosage and Administration (2.2)].
Instruct patients that when injecting TRESIBA, they must press and hold down the dose button until the dose counter shows 0 and then keep the needle in the skin and count slowly to 6. When the dose counter returns to 0, the prescribed dose is not completely delivered until 6 seconds later. If the needle is removed earlier, they may see a stream of insulin coming from the needle tip. If so, the full dose will not be delivered (a possible under-dose may occur by as much as 20%), and they should increase the frequency of checking their blood glucose levels and possible additional insulin administration may be necessary.
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If 0 does not appear in the dose counter after continuously pressing the dose button, the patient may have used a blocked needle. In this case they would not have received any insulin � even though the dose counter has moved from the original dose that was set.
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If the patient did have a blocked or damaged needle, instruct them to change the needle as described in Step 15 of the Instructions for Use and repeat all steps in the IFU starting with a new needle and the Section Preparing your TRESIBA FlexTouch Pen. Make sure the patient selects the full dose needed.
If patients routinely do not hold the needle under the skin as recommended, the patient may need to slightly increase the dialed insulin dose to achieve the patient's glycemic targets.
Instruct patients to not re-use needles. A new needle must be attached before each injection. Reuse of needles increases the risk of blocked needles which may cause under-dosing or overdosing.
Instruct Patients to never use a syringe to remove TRESIBA from the FlexTouch disposable insulin prefilled pen.
Administration
TRESIBA must only be used if the solution is clear and colorless with no particles visible.
Patients must be advised that TRESIBA must NOT be diluted or mixed with any other insulin or solution [see Dosage and Administration (2.1)].
Management of Hypoglycemia and Handling of Special Situations
Patients should be instructed on self-management procedures including glucose monitoring, proper injection technique, and management of hypoglycemia and hyperglycemia. Patients must be instructed on handling of special situations such as intercurrent conditions (illness, stress, or emotional disturbances), an inadequate or skipped insulin dose, inadvertent administration of an increased insulin dose, inadequate food intake, and skipped meals [see Warnings and Precautions (5.3)].
Refer patients to the TRESIBA "Patient Information" for additional information about the potential side effects of insulin therapy, including lipodystrophy (and the need to rotate injection sites within the same body region), weight gain, allergic reactions, and hypoglycemia.
Women of Reproductive Potential
Advise patients to inform their health care professional if they are pregnant or are contemplating pregnancy.
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