Truvelog 100 U Solution for injection

TRUVELOG is indicated for the treatment of diabetes mellitus in adults, adolescents and children aged 1 year and above.

Posology
The potency of insulin analogues, including insulin aspart, is expressed in units, whereas the potency of human insulin is expressed in international units. TRUVELOG dosing is individual and determined in accordance with the needs of the patient. It should normally be used in combination with intermediate-acting or long-acting insulin. Blood glucose monitoring and insulin dose adjustments are recommended to achieve optimal glycaemic control. The individual insulin requirement in adults and children is usually between 0,5 and 1 units/kg/day. In a basal-bolus treatment regimen 50-70 % of this requirement may be provided by TRUVELOG and the remainder by intermediate-acting or long-acting insulin. Adjustment of dose may be necessary if patients undertake increased physical activity, change their usual diet or during concomitant illness.
Transfer from other insulin medicines
When transferring from other insulin medicines, adjustment of the TRUVELOG dose and the dose of the basal insulin may be necessary. TRUVELOG has a faster onset and a shorter duration of action than soluble human insulin. When injected subcutaneously into the abdominal wall, the onset of action will occur within 10-20 minutes of injection. The maximum effect is exerted between 1 and 3 hours after the injection. The duration of action is 3 to 5 hours.
Close glucose monitoring is recommended during the transfer and in the initial weeks thereafter (see section 4.4).
Special populations
Elderly
TRUVELOG can be used in elderly patients. In elderly patients, glucose monitoring should be intensified and the TRUVELOG dose adjusted on an individual basis.
Renal impairment
Renal impairment may reduce the patientu2019s insulin requirements. In patients with renal impairment, glucose monitoring should be intensified and the insulin aspart dose adjusted on an individual basis.
Hepatic impairment
Hepatic impairment may reduce the patientu2019s insulin requirements. In patients with hepatic impairment, glucose monitoring should be intensified and the TRUVELOG dose adjusted on an individual basis.
Paediatric population
TRUVELOG can be used in adolescents and children aged 1 year and above in preference to soluble human insulin when a rapid onset of action might be beneficial, for example, in the timing of the injections in relation to meals (see sections 5.1 and 5.2). The safety and efficacy of TRUVELOG in children below 1 year of age have not been established. No data are available.
Method of administration
TRUVELOG is for subcutaneous use. Insulin aspart is a rapid-acting insulin analogue. TRUVELOG is administered subcutaneously by injection in the upper arms, thighs, buttocks or abdomen. Injection sites should always be rotated within the same region in order to reduce the risk of lipodystrophy. Subcutaneous injection in the abdominal wall ensures a faster absorption than other injection sites. Compared to soluble human insulin the faster onset of action of insulin aspart is maintained regardless of the injection site. The duration of action will vary according to the dose, injection site, blood flow, temperature and level of physical activity. Due to the faster onset of action, insulin aspart should generally be given immediately before a meal. When necessary insulin aspart can be given soon after a meal.
Injecting a dose
1. Wash your hands.
2. Choose a site for injection.
3. Clean the skin as instructed.
4. Remove outer needle cap.
5. Stabilise the skin by spreading it or pinching up a large area. Insert the needle as instructed.
6. Press the knob.
7. Pull the needle out and apply gentle pressure over the injection site for several seconds. Do not rub the area.
8. Using the outer needle cap, unscrew the needle and dispose of it safely.
9. Use of injection sites should be rotated so that the same site is not used more than approximately once a month.
TRUVELOG solution for injection in cartridge
TRUVELOG in cartridges is only suitable for subcutaneous injections from a reusable pen. If administration by syringe, intravenous injection or infusion pump is necessary, a vial should be used. Other insulin aspart medicines offering such an option should be used. TRUVELOG in cartridges is designated to be used in the following pens (see section 6.6).
u2022 JuniorSTAR which delivers 1-30 units of insulin aspart in 0,5 unit dose increments.
u2022 Tactipen which delivers 1-60 units of insulin aspart in 1 unit dose increments.
u2022 AllStar and AllStar PRO which all deliver 1-80 units of insulin aspart in 1 unit dose increments.
TRUVELOG solution for injection in pre-filled pen
TRUVELOG in pre-filled pen is only suitable for subcutaneous injections. If administration by syringe, intravenous injection or infusion pump is necessary, a vial should be used. Other insulin aspart medicines offering such an option should be used. TRUVELOG in pre-filled pen delivers 1-80 units in increments of 1 unit. Patients must visually verify the dialled units on the dose counter of the pen. Therefore, the requirement for patients with self-inject is that they can read the dose counter on the pen. Patients who are blind or have poor vision must be instructed to always get help/assistance from another person who has good vision and is trained in using the insulin device. For detailed user instructions, please refer to the patient information leaflet.

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

Traceability
In order to improve the traceability of biological medicines, the name and the batch number of the administered product should be clearly recorded.
Hyperglycaemia
Inadequate dosing or discontinuation of treatment, especially in type 1 diabetes, may lead to hyperglycaemia and diabetic ketoacidosis. Usually the first symptoms of hyperglycaemia develop gradually over a period of hours or days. They include thirst, increased frequency of urination, nausea, vomiting, drowsiness, flushed dry skin, dry mouth, loss of appetite as well as acetone odour of breath. In type 1 diabetes, untreated hyperglycaemic events eventually lead to diabetic ketoacidosis, which is potentially lethal.
Hypoglycaemia
Omission of a meal or unplanned, strenuous physical exercise may lead to hypoglycaemia. Especially in children, care should be taken to match insulin doses (especially in basal-bolus regimens) with food intake, physical activities and current blood glucose level in order to minimise the risk of hypoglycaemia. Hypoglycaemia may occur if the insulin dose is too high in relation to the insulin requirement. In case of hypoglycaemia or if hypoglycaemia is suspected TRUVELOG must not be injected. After stabilisation of patientu2019s blood glucose adjustment of the dose should be considered (see sections 4.8 and 4.9). Patients whose blood glucose control is greatly improved, e.g. by intensified insulin therapy, may experience a change in their usual warning symptoms of hypoglycaemia, and should be advised accordingly. Usual warning symptoms may disappear in patients with longstanding diabetes. A consequence of the pharmacodynamics of rapid-acting insulin analogues is that if hypoglycaemia occurs, it may occur earlier after an injection when compared with soluble human insulin. Since TRUVELOG should be administered in immediate relation to a meal, the rapid onset of action should be considered in patients with concomitant diseases or treatment where a delayed absorption of food might be expected. Concomitant illness, especially infections and feverish conditions, usually increases the patientu2019s insulin requirements. Concomitant diseases in the kidney, liver or affecting the adrenal, pituitary or thyroid gland can require changes in the insulin dose. When patients are transferred between different types of insulin medicines, the early warning symptoms of hypoglycaemia may change or become less pronounced than those experienced with their previous insulin.
Transfer from other insulin medicines
Transferring a patient to another type or brand of insulin should be done under strict medical supervision. Changes in strength, brand (manufacturer), type, origin (animal, human insulin or human insulin analogue) and/or method of manufacture (recombinant DNA versus animal source insulin) may result in the need for a change in dose. Patients transferred to TRUVELOG from another type of insulin may require an increased number of daily injections or a change in dose from that used with their usual insulin medicines. If an adjustment is needed, it may occur with the first dose or during the first few weeks or months.
Injection site reactions
As with any insulin therapy, injection site reactions may occur and include pain, redness, hives, inflammation, bruising, swelling and itching. Continuous rotation of the injection site within a given area reduces the risk of developing these reactions. Reactions usually resolve in a few days to a few weeks. On rare occasions, injection site reactions may require discontinuation of insulin aspart.
Combination of TRUVELOG with pioglitazone
Cases of cardiac failure have been reported when pioglitazone was used in combination with insulin, especially in patients with risk factors for development of cardiac heart failure. This should be kept in mind if treatment with the combination of pioglitazone and TRUVELOG is considered. If the combination is used, 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.
Avoidance of accidental mix-ups/medication errors
Patients must be instructed to always check the insulin label before each injection to avoid accidental mix-ups between TRUVELOG and other insulin products.
Insulin antibodies
Insulin administration may cause insulin antibodies to form. In rare cases, the presence of such insulin antibodies may necessitate adjustment of the insulin dose in order to correct a tendency to hyper- or hypoglycaemia.
Travel
Before travelling between different time zones, the patient should seek the doctoru2019s advice since this may mean that the patient has to take the insulin and meals at different times.
Sodium
This medicine product contains less than 1 mmol sodium (23 mg) per dose, i.e. essentially u201csodium-freeu201d.

A number of medicines are known to interact with the glucose metabolism. The following substances may reduce the patientu2019s insulin requirements: Oral antidiabetic medicines, monoamine oxidase inhibitors (MAOI), beta-blockers, angiotensin converting enzyme (ACE) inhibitors, salicylates, anabolic steroids and sulphonamides. The following substances may increase the patientu2019s insulin requirements: Oral contraceptives, thiazides, glucocorticoids, thyroid hormones, sympathomimetics, growth hormone and danazol. Beta-blockers may mask the symptoms of hypoglycaemia. Octreotide/lanreotide may either increase or decrease the insulin requirement. Alcohol may intensify or reduce the hypoglycaemic effect of insulin.

Pregnancy
TRUVELOG (insulin aspart) can be used in pregnancy. Data from two randomised controlled clinical trials (322 and 27 exposed pregnancies) do not indicate any adverse effect of insulin aspart on pregnancy or on the health of the foetus/newborn when compared to human insulin (see section 5.1). Intensified blood glucose control and monitoring of pregnant women with diabetes (type 1 diabetes, type 2 diabetes or gestational diabetes) are recommended throughout pregnancy and when contemplating pregnancy. Insulin requirements usually fall in the first trimester and increase subsequently during the second and third trimester. After delivery, insulin requirements normally return rapidly to pre-pregnancy values.
Breastfeeding
There are no restrictions on treatment with TRUVELOG during breastfeeding. Insulin treatment of the nursing mother presents no risk to the baby. However, the TRUVELOG dose may need to be adjusted.
Fertility
Animal reproduction studies have not revealed any difference between insulin aspart and human insulin regarding fertility (see section 5.3).

The patientu2019s ability to concentrate and react may be impaired as a result of hypoglycaemia. This may constitute a risk in situations where these abilities are of special importance (e.g. driving a car or using machines). Patients should be advised to take precautions to avoid hypoglycaemia while driving, this is particularly important in those who have reduced or absent awareness of the warning signs of hypoglycaemia or have frequent episodes of hypoglycaemia. The advisability of driving should be considered in these circumstances.

Summary of the safety profile
Adverse reactions observed in patients using TRUVELOG are mainly due to the pharmacologic effect of insulin. The most frequently reported adverse reaction during treatment is hypoglycaemia. The frequencies of hypoglycaemia vary with patient population, dose regimens and level of glycaemic control (see section 4.8 Description of selected adverse reactions). At the beginning of the insulin treatment, refraction anomalies, oedema and injection site reactions (pain, redness, hives, inflammation, bruising, swelling and itching at the injection site) may occur. These reactions are usually of transitory nature. Fast improvement in blood glucose control may be associated with acute painful neuropathy, which is usually reversible. Intensification of insulin therapy with abrupt improvement of glycaemic control may be associated with temporary worsening of diabetic retinopathy, while long-term improved glycaemic control decreases the risk of progression of diabetic retinopathy.
Tabulated list of adverse reactions
Adverse reactions listed below are based on clinical trial data and classified according to System Organ Class. Frequency categories are defined according to the following convention: Very common (> 1/10); common (> 1/100 to 1/1 000 to 1/10 000 to < 1/1 000); very rare (< 1/10 000); not known (cannot be estimated from the available data).
MedDRA system organ classes
Very common
Uncommon
Rare
Very rare
Immune system disorders
Urticaria, rash, eruptions
Anaphylactic reactions*
Metabolism and nutrition disorders
Hypoglycaemia*
Nervous system disorders
Peripheral neuropathy (painful neuropathy)
Eye disorders
Refraction disorders, diabetic retinopathy
Skin and subcutaneous tissue disorders
Lipodystrophy*
General disorders and administration site conditions
Injection site reactions, oedema
* See section 4.8 Description of selected adverse reactions.
Description of selected adverse reactions
Anaphylactic reactions
The occurrence of generalised hypersensitivity reactions (including generalised skin rash, itching, sweating, gastrointestinal upset, angioneurotic oedema, difficulties in breathing, palpitation and reduction in blood pressure) is very rare but can potentially be life threatening.
Hypoglycaemia
The most frequently reported adverse reaction is hypoglycaemia. It may occur if the insulin dose is too high in relation to the insulin requirement. Severe hypoglycaemia may lead to unconsciousness and/or convulsions and may result in temporary or permanent impairment of brain function or even death. The symptoms of hypoglycaemia usually occur suddenly. They may include cold sweats, cool pale skin, fatigue, nervousness or tremor, anxiousness, unusual tiredness or weakness, confusion, difficulty in concentration, drowsiness, excessive hunger, vision changes, headache, nausea and palpitation.
In clinical trials, the frequency of hypoglycaemia varied with patient population, dose regimens and level of glycaemic control. During clinical trials the overall rates of hypoglycaemia did not differ between patients treated with insulin aspart compared to human insulin.
Skin and subcutaneous tissue disorders
Lipodystrophy (including lipohypertrophy, lipoatrophy) may occur at the injection site. Continuous rotation of the injection site within the particular injection area reduces the risk of developing these reactions.
Paediatric population
Based on post-marketing sources and clinical trials with insulin aspart, the frequency, type and severity of adverse reactions observed in the paediatric population do not indicate any differences to the broader experience in the general population.
Other special populations
Based on post-marketing sources and clinical trials with insulin aspart, the frequency, type and severity of adverse reactions observed in the elderly patients and in patients with renal or hepatic impairment do not indicate any differences to the broader experience in the general population.
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorization of the medicine is important. It allows continued monitoring of the benefit/risk balance of the medicine. Healthcare professionals are asked to report any suspected adverse reactions to: The Pharmacovigilance Unit at Sanofi: [email protected] (email) or 011 256-3700 (tel), or SAHPRA via the u201c6.04 Adverse Drug Reactions Reporting Formu201d found online under SAHPRAu2019s publications: https://www.sahpra.org.za/Publications/Index/8

A specific overdose for insulin cannot be defined, however, hypoglycaemia may develop over sequential stages if too high doses relative to the patientu2019s requirement are administered:
u2022 Mild hypoglycaemic episodes can be treated by oral administration of glucose or sugary products. It is therefore recommended that the diabetic patient always carries sugar-containing products.
u2022 Severe hypoglycaemic episodes, where the patient has become unconscious, can be treated with glucagon (0,5 to 1,0 mg) given intramuscularly or subcutaneously by a trained person, or with glucose given intravenously by physicians or other healthcare staff. Glucose must be given intravenously, if the patient does not respond to glucagon within 10 to 15 minutes. Upon regaining consciousness, administration of oral carbohydrates is recommended for the patient in order to prevent a relapse.