Dear Doctors and Pharmacists,

Novo Nordisk A/S informs about the launch of Tresiba® (insulin degludec) 100 U (100 units/mL insulin solution for injection) in a prefilled pen (FlexTouch®). 

Tresiba® is a novel basal insulin with a unique mechanism of protraction designed to provide a flat and reproducible PK/PD profile.Tresiba® is an analogue of human insulin that incorporates a fatty diacid-glutamate side-chain, which enables hexamers to link one to another1. In the injected formulation, Tresiba® assembles as stable dihexamers, but upon injection these link into long chains of hundreds of hexamers to form a soluble depot. Over time, these multihexamers release monomers at a slow and steady rate, and these smaller molecules enter the circulation readily (see figure below).1

insulin

Tresiba® has a half-life of ~25 hours – twice that of insulin glargine.2 With once-daily dosing, Tresiba® reaches a steady state that has a flat plasma concentration profile (i.e., a low peak: trough ratio), with a corresponding flat glucose-lowering response.3 The blood glucose-lowering effect endures beyond 42 hours,4 and compared with insulin glargine, there is a four-fold reduction in the variability of PD effect that a patient will experience with Tresiba® from injection to injection.5 Clinically, these PK/PD characteristics of Tresiba®  result in a significantly reduced risk of nocturnal hypoglycaemia compared with insulin glargine at equivalent HbA1c and equivalent or superior fasting glucose control.6,7

Another benefit of the long half-life and flat and stable PK/PD profile of Tresiba® is that some flexibility in dose timing should be possible because day-to-day inconsistencies in administration time would have only a minor impact on plasma kinetics.6 Studies have tested this and shown that Tresiba® given at alternating intervals of 8 and 40 hours remains as effective and well tolerated as insulin glargine dosed, per label, at the same time each day.8,9

In conclusion, the unique mode of protraction of Tresiba® translates clinically into a predictable glucose-lowering effect, with a lower risk of nocturnal hypoglycaemia versus glargine and the potential to vary dosing time if needed (although with a minimum of 8 hours between injections).10

Important information when initiating Tresiba®:

Simple to start and simple to switch10

Initiation

Patients with type 2 diabetes mellitus
The recommended daily starting dose is 10 units followed by individual dosage adjustments.

Patients with type 1 diabetes mellitus
Tresiba® is to be used once-daily with meal-time insulin and requires subsequent individual dosage adjustments.

Transfer from other insulin medicinal products

Close glucose monitoring is recommended during the transfer and in the following weeks. Doses and timing of concurrent rapid-acting or short-acting insulin products or other concomitant anti‑diabetic treatment may need to be adjusted.

Patients with type 2 diabetes mellitus
For patients with type 2 diabetes taking basal, basal-bolus, premix or self-mixed insulin therapy, changing the basal insulin to Tresiba® can be done unit-to-unit based on the previous basal insulin dose followed by individual dosage adjustments. 

Patients with type 1 diabetes mellitus
For most patients with type 1 diabetes, changing the basal insulin to Tresiba® can be done unit-to-unit based on the previous basal insulin dose with subsequent individual dosage adjustments. For patients with type 1 diabetes transferring from twice-daily basal insulin or having HbA1c < 8.0% at the time of transfer, the dose of Tresiba® needs to be determined on an individual basis. Dose reduction needs to be considered followed by individual dosage adjustment based on the glycaemic response.
 

Tresiba® also brings to Malta a new pre-filled pen for the administration of insulin: FlexTouch®

Download Tresiba® SPC

flextouch

Abbreviated prescribing information

arrow.gif   This medicinal product is subject to additional monitoring.

Tresiba® (insulin degludec) 100 U (100 units/mL insulin solution for injection) in a prefilled pen (FlexTouch®) Consult Summary of Product Characteristics before prescribing. Presentation: Tresiba® FlexTouch®. Tresiba® 100 units/mL – 1 mL of solution contains 100 units insulin degludec (equivalent to 3.66 mg insulin degludec). One pre-filled device contains 300 units of insulin degludec in 3 mL solution. The pre filled pen (FlexTouch®) is designed to be used with NovoFine®/NovoTwist® injection needles up to a length of 8 mm. It delivers 1-80 units in steps of 1 unit. Detailed instructions accompanying the pre filled pen must be followed. Indications: Treatment of diabetes mellitus in adults. Posology and administration: Tresiba® is a basal insulin for once-daily subcutaneous administration any time of the day, preferably at the same time of day. On occasions when administration at the same time of the day is not possible, Tresiba® allows for flexibility in the timing of insulin administration. A minimum of 8 hours between injections should be ensured. In patients with type 2 diabetes mellitus, Tresiba® can be administered alone or in any combination with oral anti diabetic medicinal products, GLP-1 receptor agonists and bolus insulin. When adding Tresiba® to GLP-1 receptor agonists, the recommended daily starting dose is 10 units followed by individual dosage adjustments. When adding GLP-1 receptor agonists to Tresiba®, it is recommended to reduce the dose of Tresiba® by 20% to minimise the risk of hypoglycaemia. Subsequently, dosage should be adjusted individually. In patient with type 1 diabetes mellitus, Tresiba® is to be used with short-/rapid-acting insulin. Administration by subcutaneous injection only. Tresiba® is to be used once-daily with meal-time insulin and requires subsequent individual dosage adjustments. For most patients with type 1 diabetes, changing the basal insulin to Tresiba® can be done unit-to-unit based on the previous basal insulin dose with subsequent individual dosage adjustments. . For patients with type 1 diabetes transferring from twice-daily basal insulin or having HbA1c < 8.0% at the time of transfer, the dose of Tresiba® needs to be determined on an individual basis. Dose reduction needs to be considered followed by individual dosage adjustment based on the glycaemic response. Transferring from other insulins; Close glucose monitoring is recommended during the transfer and in the following weeks. Doses and timing of concurrent rapid-acting or short-acting insulin products or other concomitant anti diabetic treatment may need to be adjusted. In elderly patients and patients with renal/hepatic impairment glucose monitoring should be intensified and the dose adjusted on an individual basis. The safety/efficacy of Tresiba® has not been established in adolescents/children below 18 yrs. of age. Contraindications: Hypersensitivity to the active substance or any of the excipients. Special warnings and precautions: Too high insulin dose, omission of a meal or unplanned strenuous physical exercise may lead to hypoglycaemia. Reduction of warning symptoms of hypoglycaemia may be seen upon tightening control and also in patients with long-standing diabetes. Administration of rapid-acting insulin recommended in situations with severe hyperglycaemia. Inadequate dosing and/or discontinuation of treatment in patients requiring insulin may lead to hyperglycaemia and potentially to diabetic ketoacidosis. Concomitant illness, especially infections, may lead to hyperglycaemia and thereby cause an increased insulin requirement. Transferring to a new type, brand or manufacturer of insulin should be done under strict medical supervision. When using insulin in combination with pioglitazone, patients should be observed for signs and symptoms of heart failure, weight gain and oedema. Pioglitazone should be discontinued if any deterioration in cardiac symptoms occurs. Patients must be instructed to always check the insulin label before each injection to avoid accidental mix-ups between the two strengths of Tresiba® and other insulins. Hypoglycaemia may constitute a risk when driving or operating machinery. Pregnancy, lactation and fertility: There is no clinical experience with use of Tresiba® in pregnant women and during breastfeeding. Animal reproduction studies with insulin degludec have not revealed any adverse effects on fertility. Undesirable effects: Refer to SmPC for complete information on side effects. Very common (≥1/10); common (≥1/100 to < 1/10); uncommon (≥1/1.000 to < 1/100); rare (≥ 1/10.000 to < 1/1.000); very rare (< 1/10.000); not known (cannot be estimated from the available data). Very common: Hypoglycaemia. Common: Injection site reactions. Uncommon: Lipodystrophy and peripheral oedema. Rare: Hypersensitivity and urticaria. With insulin preparations, allergic reaction may occur; immediate-type allergic reactions may potentially be life threatening. Injection site reactions are usually mild, transitory and normally disappear during continued treatment. Marketing authorisation numbers: Tresiba® FlexTouch® 100 U/mL EU/1/12/807/004 (5 pre-filled pens). Legal category: Prescription-only medicine (POM). Marketing authorisation holder: Novo Nordisk A/S Novo Alle DK-2880 Bagsvard Denmark. Date of Review of Prescribing Information: April 2014. Summary of Product Characteristics can be obtained from Novo Nordisk A/S.

1. Jonassen I et al. Pharm Res 2012;29:2104–14; 2.  Heise T et al. Diabetes 2011;60(Suppl. 1A):LB11; 3. Heise T et al. Diabetes Obes Metab 2012;14:944–50; 4. Kurtzhals P et al. Diabetes 2011;60(Suppl. 1A):LB12; 5. Heise T et al. Diabetes Obes Metab 2012;14:859–64; 6. Gough S et al. Diabetes Obes Metab 2012;15:301–9; 7. Ratner R et al. Diabetes Obes Metab 2013;15:175–84; 8. Mathieu C et al. J Clin Endocrinol Metab 2013;98:1154–62;9. Meneghini L et al. Diabetes Care 2013;36:858–64; 10. Novo Nordisk A/S. Tresiba® (Insulin degludec) Summary of Product Characteristics;

Legal Category: POM; Public price 118,00 €

Suspected adverse reactions and medication errors should be reported. Report forms can be downloaded from www.medicinesauthority/adrportal and sent by post or email to:

P: ADR reporting/ 203, level 3 Rue D’Argens Gzira GZR 1368

E: postlicensing.medicinesauthority@gov.mt 

IT/TRE/0614/0015.

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