- 1. Name of the medicinal product
- 2. Qualitative and quantitative composition
- 3. Pharmaceutical form
- 4. Clinical particulars
- 4.1 Therapeutic indications
- 4.2 Posology and method of administration
- 4.3 Contraindications
- 4.4 Special warnings and precautions for use
- 4.5 Interaction with other medicinal products and other forms of interaction
- 4.6 Fertility, pregnancy and lactation
- 4.7 Effects on ability to drive and use machines
- 4.8 Undesirable effects
- 4.9 Overdose
- 5. Pharmacological properties
- 5.1 Pharmacodynamic properties
- 5.2 Pharmacokinetic properties
- 5.3 Preclinical safety data
- 6. Pharmaceutical particulars
- 6.1 List of excipients
- 6.2 Incompatibilities
- 6.3 Shelf life
- 6.4 Special precautions for storage
- 6.5 Nature and contents of container
- 6.6 Special precautions for disposal and other handling
- 7. Marketing authorisation holder
- 8. Marketing authorisation number(s)
- 9. Date of first authorisation/renewal of the authorisation
- 10. Date of revision of the text
PosologyThe desired blood glucose levels, the insulin preparations to be used and the insulin dose regimen (doses and timings) must be determined individually and adjusted to suit the patient's diet, physical activity and life-style.
Daily doses and timing of administrationThere are no fixed rules for insulin dose regimen. However, the average insulin requirement is often 0.5 to 1.0 IU per kg body weight per day. The basal metabolic requirement is 40% to 60% of the total daily requirement. Insuman Comb 25 is injected subcutaneously 30 to 45 minutes before a meal.SoloStar delivers insulin in doses from 1 to 80 units in steps of 1 unit. Each pen contains multiple doses.
Secondary dose adjustmentImproved metabolic control may result in increased insulin sensitivity, leading to a reduced insulin requirement. Dose adjustment may also be required, for example, if- the patient's weight changes,- the patient's life-style changes,- other circumstances arise that may promote an increased susceptibility to hypo- or hyperglycaemia (see section 4.4).
Elderly population ( ≧65 years old)In the elderly, progressive deterioration of renal function may lead to a steady decrease in insulin requirements.
Renal impairmentIn patients with renal impairment, insulin requirements may be diminished due to reduced insulin metabolism.
Hepatic impairmentIn patients with severe hepatic impairment, insulin requirements may be diminished due to reduced capacity for gluconeogenesis and reduced insulin metabolism.
Method of administrationInsuman Comb 25 is administered subcutaneously. Insuman Comb 25 must never be injected intravenously.Insulin absorption and hence the blood-glucose-lowering effect of a dose may vary from one injection area to another (e.g. the abdominal wall compared with the thigh). Injection sites within an injection area must be rotated from one injection to the next.Before using SoloStar, the Instructions for Use included in the Package Leaflet must be read carefully. For further details on handling, see section 6.6.
Transfer to Insuman Comb 25Transferring a patient to another type or brand of insulin should be done under strict medical supervision. Changes in strength, brand (manufacturer), type (regular, NPH, lente, long-acting, etc.), origin (animal, human, human insulin analogue) and/or method of manufacture may result in the need for a change in dose.The need to adjust (e.g. reduce) the dose may become evident immediately after transfer. Alternatively, it may emerge gradually over a period of several weeks.Following transfer from an animal insulin to human insulin, dose regimen reduction may be required in particular in patients who- were previously already controlled on rather low blood glucose levels,- have a tendency to hypoglycaemia,- previously required high insulin doses due to the presence of insulin antibodies.Close metabolic monitoring is recommended during the transition and in the initial weeks thereafter. In patients who require high insulin doses because of the presence of insulin antibodies, transfer under medical supervision in a hospital or similar setting must be considered.HypoglycaemiaHypoglycaemia may occur if the insulin dose is too high in relation to the insulin requirement.Particular caution should be exercised, and intensified blood glucose monitoring is advisable in patients in whom hypoglycaemic episodes might be of particular clinical relevance, such as in patients with significant stenoses of the coronary arteries or of the blood vessels supplying the brain (risk of cardiac or cerebral complications of hypoglycaemia) as well as in patients with proliferative retinopathy, particularly if not treated with photocoagulation (risk of transient amaurosis following hypoglycaemia).Patients should be aware of circumstances where warning symptoms of hypoglycaemia are diminished. The warning symptoms of hypoglycaemia may be changed, be less pronounced or be absent in certain risk groups. These include patients:- in whom glycaemic control is markedly improved,- in whom hypoglycaemia develops gradually,- who are elderly,- after transfer from animal insulin to human insulin,- in whom an autonomic neuropathy is present,- with a long history of diabetes,- suffering from a psychiatric illness,- receiving concurrent treatment with certain other medicinal products (see section 4.5).Such situations may result in severe hypoglycaemia (and possibly loss of consciousness) prior to the patient's awareness of hypoglycaemia.If normal or decreased values for glycated haemoglobin are noted, the possibility of recurrent, unrecognised (especially nocturnal) episodes of hypoglycaemia must be considered.Adherence of the patient to the dose regimen and dietary regimen, correct insulin administration and awareness of hypoglycaemia symptoms are essential to reduce the risk of hypoglycaemia. Factors increasing the susceptibility to hypoglycaemia require particularly close monitoring and may necessitate dose adjustment. These include:- change in the injection area,- improved insulin sensitivity (e.g. by removal of stress factors),- unaccustomed, increased or prolonged physical activity,- intercurrent illness (e.g. vomiting, diarrhoea),- inadequate food intake,- missed meals,- alcohol consumption,- certain uncompensated endocrine disorders (e.g. in hypothyroidism and in anterior pituitary or adrenocortical insufficiency),- concomitant treatment with certain other medicinal products.
Intercurrent illnessIntercurrent illness requires intensified metabolic monitoring. In many cases, urine tests for ketones are indicated, and often it is necessary to adjust the insulin dose. The insulin requirement is often increased. Patients with type 1 diabetes must continue to consume at least a small amount of carbohydrates on a regular basis, even if they are able to eat only little or no food, or are vomiting etc. and they must never omit insulin entirely.
Handling of the penBefore using SoloStar, the Instructions for Use included in the Package Leaflet must be read carefully. SoloStar has to be used as recommended in these Instructions for Use (see section 6.6).
Medication errorsMedication errors have been reported in which other Insuman formulations or other insulins have been accidentally administered. Insulin label must always be checked before each injection to avoid medication errors between insulin human and other insulins.
Combination of Insuman with pioglitazoneCases 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 Insuman 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.
PregnancyFor insulin human, no clinical data on exposed pregnancies are available. Insulin does not cross the placental barrier. Caution should be exercised when prescribing to pregnant women.It is essential for patients with pre-existing or gestational diabetes to maintain good metabolic control throughout pregnancy. Insulin requirements may decrease during the first trimester and generally increase during the second and third trimesters. Immediately after delivery, insulin requirements decline rapidly (increased risk of hypoglycaemia). Careful monitoring of glucose control is essential.Breast-feedingNo effects on the suckling child are anticipated. Insuman Comb 25 can be used during breast-feeding. Breast-feeding women may require adjustments in insulin dose and diet.
FertilityNo clinical or animal data with insulin human on male or female fertility are available.
Summary of the safety profileHypoglycaemia, in general the most frequent adverse reaction of insulin therapy, may occur if the insulin dose is too high in relation to the insulin requirement. In clinical studies and during marketed use, the frequency varies with patient population and dose regimens. Therefore, no specific frequency can be presented.
Tabulated list of adverse reactionsThe following related adverse reactions from clinical investigations are listed below by system organ class and in order of decreasing incidence: 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).Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.
|MedDRA system organ classes||Common||Uncommon||Not known|
|Immune system disorders||Shock||Immediate type allergic reactions (hypotension, angioneurotic oedema, bronchospasm, generalised skin reactions); Anti-insulin antibodies|
|Metabolism and nutrition disorders||Oedema||Hypoglycaemia; Sodium retention|
|Eye disorders||Proliferative retinopathy; Diabetic retinopathy; Visual impairment|
|Skin and subcutaneous tissue disorders||Lipodystrophy|
|General disorders and administration site conditions||Injection site reactions||Injection site urticaria||Injection site inflammation; Injection site pain; Injection site pruritus; Injection site erythema; Injection site swelling|
Description of selected adverse reactions
Immune system disordersImmediate type allergic reactions to insulin or to the excipients may be life-threatening. Insulin administration may cause anti-insulin antibodies to form. In rare cases, the presence of such anti-insulin antibodies may necessitate adjustment of the insulin dose in order to correct a tendency to hyper- or hypoglycaemia.
Metabolism and nutrition disordersSevere hypoglycaemic attacks, especially if recurrent, may lead to neurological damage.Prolonged or severe hypoglycaemic episodes may be life-threatening.In many patients, the signs and symptoms of neuroglycopenia are preceded by signs of adrenergic counter-regulation. Generally, the greater and more rapid the decline in blood glucose, the more marked is the phenomenon of counter-regulation and its symptoms.Insulin may cause sodium retention and oedema, particularly if previously poor metabolic control is improved by intensified insulin therapy.
Eyes disordersA marked change in glycaemic control may cause temporary visual impairment, due to temporary alteration in the turgidity and refractive index of the lens.Long-term improved glycaemic control decreases the risk of progression of diabetic retinopathy. However, intensification of insulin therapy with abrupt improvement in glycaemic control may be associated with temporary worsening of diabetic retinopathy.
Skin and subcutaneous tissue disordersLipodystrophy may occur at the injection site and delay local insulin absorption. Continuous rotation of the injection site within the given injection area may help to reduce or prevent these reactions.
General disorders and administration site conditionsMost minor reactions to insulins at the injection site usually resolve in a few days to a few weeks.
Reporting of suspected adverse reactionsReporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard.
Mechanism of actionInsulin- lowers blood glucose and promotes anabolic effects as well as decreasing catabolic effects,- increases the transport of glucose into cells as well as the formation of glycogen in the muscles and the liver, and improves pyruvate utilisation. It inhibits glycogenolysis and gluconeogenesis,- increases lipogenesis in the liver and adipose tissue and inhibits lipolysis,- promotes the uptake of amino acids into cells and promotes protein synthesis, - enhances the uptake of potassium into cells.
Pharmacodynamic effectsInsuman Comb 25 (a biphasic isophane insulin suspension with 25% dissolved insulin) is an insulin with gradual onset and long duration of action. Following subcutaneous injection, onset of action is within 30 to 60 minutes, the phase of maximum action is between 2 and 4 hours after injection and the duration of action is 12 to 19 hours.
Mixing of insulinsInsuman Comb 25 must not be mixed with any other insulin or with insulin analogues.Care must be taken to ensure that no alcohol or other disinfectants enter the insulin suspension.
Shelf life after first use of the penThe pen in-use or carried as a spare may be stored for a maximum of 4 weeks not above 25°C and away from direct heat or direct light.Pens in-use must not be stored in the refrigerator.The pen cap must be put back on the pen after each injection in order to protect from light.
Not in-use pensStore in a refrigerator (2°C - 8°C).Do not freeze. Do not put Insuman Comb 25 next to the freezer compartment or a freezer pack.Keep the pre-filled pen in the outer carton in order to protect from light.
In-use pensFor storage conditions after first opening of the medicinal product, see section 6.3.
Step 1. Check the insulinThe label on the pen should be checked to make sure it contains the correct insulin. Insuman SoloStar is white with a colour on the injection button. The injection button colour will vary based on the formulation of Insuman insulin used. After removing the pen cap, the appearance of the insulin should also be checked: The insulin suspensions (Insuman Basal or Insuman mixtures) should be mixed by turning SoloStar up and down at least 10 times to resuspend the insulin. The pen should be turned gently to avoid foaming in the cartridge. After mixing, the insulin suspensions must have an evenly milky-white appearance.
Step 2. Attach the needleOnly needles that are compatible for use with SoloStar should be used.A new sterile needle will be always used for each injection. After removing the cap, the needle should be carefully attached straight onto the pen. Step 3. Perform a safety testPrior to each injection, a safety test has to be performed to ensure that pen and needle work properly and to remove air bubbles.A dose of 2 units has to be selected.The outer and inner needle caps should be removed.While holding the pen with the needle pointing upwards, the insulin reservoir should be tapped gently with the finger so that any air bubbles rise up towards the needle.Then the injection button should be pressed in completely.If insulin has been expelled through the needle tip, then the pen and the needle are working properly. If no insulin appears at the needle tip, step 3 should be repeated until insulin appears at the needle tip. Step 4. Select the doseThe dose can be set in steps of 1 unit, from a minimum of 1 unit to a maximum of 80 units. If a dose greater than 80 units is required, it should be given as two or more injections.The dose window must show 0 following the safety test. The dose can then be selected. Step 5. Inject the doseThe patient should be informed on the injection technique by his health care professional. The needle should be inserted into the skin.The injection button should be pressed in completely. Then the injection button should be held down 10 seconds before withdrawing the needle. This ensures that the full dose of insulin has been injected.
Step 6. Remove and discard the needleThe needle should always be removed after each injection and discarded. This helps prevent contamination and/or infection, entry of air into the insulin reservoir and leakage of insulin. Needles mut not be re-used.Special caution must be taken when removing and disposing of the needle. Recommended safety measures for removal and disposal of needles must be followed (e.g. a one handed capping technique) in order to reduce the risk of accidental needle injury and transmission of infectious diseases.The pen cap should be replaced on the pen.
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