- 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
Excipient with known effect:Insulatard contains less than 1 mmol sodium (23 mg) per dose, i.e. Insulatard is essentially 'sodium-free'.For the full list of excipients, see section 6.1.
PosologyThe potency of human insulin is expressed in international units.Insulatard dosing is individual and determined in accordance with the needs of the patient. The physician determines whether one or several daily injections are necessary. Insulatard may be used alone or mixed with fast-acting insulin. In intensive insulin therapy the suspension may be used as basal insulin (evening and/or morning injection) with fast-acting insulin given at meals. Blood glucose monitoring is recommended to achieve optimal glycaemic control.The individual insulin requirement is usually between 0.3 and 1.0 international unit/kg/day. Adjustment of dose may be necessary if patients undertake increased physical activity, change their usual diet or during concomitant illness.
Elderly (≥ 65 years old)Insulatard can be used in elderly patients.In elderly patients, glucose monitoring should be intensified and the insulin dose adjusted on an individual basis.
Renal and hepatic impairmentRenal or hepatic impairment may reduce the patient's insulin requirements.In patients with renal or hepatic impairment, glucose monitoring should be intensified and the human insulin dose adjusted on an individual basis.
Paediatric populationInsulatard can be used in children and adolescents.
Transfer from other insulin medicinal productsWhen transferring from other intermediate or long-acting insulin medicinal products, adjustment of the Insulatard dose and timing of administration may be necessary.Close glucose monitoring is recommended during the transfer and in the initial weeks thereafter (see section 4.4).
Method of administrationInsulatard is a long-acting human insulin. Insulatard is administered subcutaneously by injection in the thigh, the abdominal wall, the gluteal region or the deltoid region. Insulin suspensions are never to be administered intravenously.Injection into a lifted skin fold minimises the risk of unintended intramuscular injection.The needle should be kept under the skin for at least 6 seconds to make sure the entire dose is injected. Injection sites should always be rotated within the same region in order to reduce the risk of lipodystrophy. Subcutaneous injection into the thigh results in a slower and less variable absorption compared to the other injection sites. The duration of action will vary according to the dose, injection site, blood flow, temperature and level of physical activity.Insulin suspensions are not to be used in insulin infusion pumps.
Administration with a syringeInsulatard vials are for use with insulin syringes with a corresponding unit scale.Insulatard vial is accompanied by a package leaflet with detailed instructions for use to be followed.
Administration with an insulin delivery systemInsulatard Penfill is designed to be used with Novo Nordisk insulin delivery systems and NovoFine or NovoTwist needles. Insulatard Penfill is accompanied by a package leaflet with detailed instructions for use to be followed.
Administration with InnoLetInsulatard InnoLet is a pre-filled pen designed to be used with NovoFine or NovoTwist disposable needles up to a length of 8 mm.InnoLet delivers 1-50 units in increments of 1 unit.Insulatard InnoLet is accompanied by a package leaflet with detailed instructions for use to be followed.
HyperglycaemiaInadequate 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.
HypoglycaemiaOmission of a meal or unplanned, strenuous physical exercise may lead to 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, Insulatard must not be injected. After stabilisation of the patient's 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.Concomitant illness, especially infections and feverish conditions, usually increases the patient's insulin requirement. 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 medicinal products, the early warning symptoms of hypoglycaemia may change or become less pronounced than those experienced with their previous insulin.
Transfer from other insulin medicinal productsTransferring a patient to another type or brand of insulin should be done under strict medical supervision. Changes in strength, brand (manufacturer), type, origin (animal insulin, human insulin or insulin analogue) and/or method of manufacture (recombinant DNA versus animal source insulin) may result in a need for a change in dose. Patients transferred to Insulatard 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 medicinal products. If an adjustment is needed, it may occur with the first dose or during the first few weeks or months.
Injection site reactionsAs 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 Insulatard.
Combination of Insulatard 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 Insulatard 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.
PregnancyThere are no restrictions on treatment of diabetes with insulin during pregnancy, as insulin does not pass the placental barrier.Both hypoglycaemia and hyperglycaemia, which can occur in inadequately controlled diabetes therapy, increase the risk of malformations and death in utero. Intensified blood glucose control and monitoring of pregnant women with 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 trimesters. After delivery, insulin requirements normally return rapidly to pre-pregnancy values.
Breast-feedingThere is no restriction on treatment with Insulatard during breast-feeding. Insulin treatment of the nursing mother presents no risk to the baby. However, the Insulatard dose may need to be adjusted.
FertilityAnimal reproduction studies with human insulin have not revealed any adverse effects on fertility.
Summary of the safety profileThe most frequently reported adverse reaction during treatment is hypoglycaemia. The frequencies of hypoglycaemia vary with patient population, dose regimens and level of glycaemic control, please see Description of selected adverse reactions below.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 in 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 reactionsThe adverse reactions listed below are based on clinical trial data and classified according to MedDRA frequency and System Organ Class. Frequency categories are defined according to the following convention: 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).
|Immune system disorders||Uncommon Urticaria, rash|
|Very rare Anaphylactic reactions*|
|Metabolism and nutrition disorders||Very common Hypoglycaemia*|
|Nervous system disorders||Very rare Peripheral neuropathy (painful neuropathy)|
|Eye disorders||Very rare Refraction disorders|
|Uncommon Diabetic retinopathy|
|Skin and subcutaneous tissue disorders||Uncommon Lipodystrophy*|
|General disorders and administration site conditions||Uncommon Injection site reactions|
Description of selected adverse reactions
Anaphylactic reactionsThe occurrence of generalised hypersensitivity reactions (including generalised skin rash, itching, sweating, gastrointestinal upset, angioneurotic oedema, difficulty in breathing, palpitation and reduction in blood pressure) is very rare but can potentially be life threatening.
HypoglycaemiaThe 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 concentrating, 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.
LipodystrophyLipodystrophy (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 populationBased on post-marketing sources and clinical trials, 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 populationsBased on post-marketing sources and clinical trials, the frequency, type and severity of adverse reactions observed in 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 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
United KingdomYellow Card SchemeWebsite: www.mhra.gov.uk/yellowcard
IrelandHPRA PharmacovigilanceEarlsfort Terrace IRL - Dublin 2Tel: +353 1 6764971Fax: +353 1 6762517Website: www.hpra.iee-mail: email@example.com
MaltaADR ReportingThe Medicines Authority Post-Licensing Directorate203 Level 3, Rue D'ArgensGŻR-1368 GżiraWebsite: www.medicinesauthority.gov.mte-mail: firstname.lastname@example.org
Mechanism of action and pharmacodynamic effectsThe blood glucose lowering effect of insulin is due to the facilitated uptake of glucose following binding of insulin to receptors on muscle and fat cells and to the simultaneous inhibition of glucose output from the liver.Insulatard is a long-acting insulin.Onset of action is within 1½ hours, reaches a maximum effect within 412 hours and the entire duration of action is approximately 24 hours.
AbsorptionThe maximum plasma concentration of the insulin is reached within 218 hours after subcutaneous administration.
DistributionNo profound binding to plasma proteins, except circulating insulin antibodies (if present) has been observed.
MetabolismHuman insulin is reported to be degraded by insulin protease or insulin-degrading enzymes and possibly protein disulfide isomerase. A number of cleavage (hydrolysis) sites on the human insulin molecule have been proposed; none of the metabolites formed following the cleavage are active.
EliminationThe terminal half-life is determined by the rate of absorption from the subcutaneous tissue. The terminal half-life (t½) is therefore a measure of the absorption rather than of the elimination per se of insulin from plasma (insulin in the blood stream has a t½ of a few minutes). Trials have indicated a t½of about 510 hours.
Insulatard vial:During use or when carried as a spare: The product can be stored for a maximum of 6 weeks. Store below 25°C.
Insulatard Penfill and Insulatard InnoLet:During use or when carried as a spare: The product can be stored for a maximum of 6 weeks. Store below 30°C.
Insulatard vial:During use or when carried as a spare: Store below 25°C. Do not refrigerate or freeze.Keep the vial in the outer carton in order to protect from light.
Insulatard Penfill:During use or when carried as a spare: Store below 30°C. Do not refrigerate or freeze.Keep the cartridge in the outer carton in order to protect from light.
Insulatard InnoLet:During use or when carried as a spare: Store below 30°C. Do not refrigerate or freeze.Keep the pen cap on InnoLet in order to protect from light.
Insulatard vial:Vial (type 1 glass) closed with a disc (bromobutyl/polyisoprene rubber) and a protective tamper-proof plastic cap containing 10 ml of suspension.Pack sizes of 1 and 5 vials of 10 ml or a multipack of 5 packs of 1 x 10 ml vial.Not all pack sizes may be marketed.
Insulatard Penfill:Cartridge (type 1 glass) with a plunger (bromobutyl) and a rubber closure (bromobutyl/polyisoprene) containing 3 ml of suspension. The cartridge contains a glass ball to facilitate resuspension.Pack sizes of 1, 5 and 10 cartridges. Not all pack sizes may be marketed.
Insulatard InnoLet:Cartridge (type 1 glass) with a plunger (bromobutyl) and a rubber closure (bromobutyl/polyisoprene) containing 3 ml of suspension in a pre-filled multidose disposable pen made of polypropylene. The cartridge contains a glass ball to facilitate resuspension.Pack sizes of 1, 5 and 10 pre-filled pens. Not all pack sizes may be marketed.
|Insulatard 100 international units/ml||EU/1/02/233/003; EU/1/02/233/004; EU/1/02/233/017|
|Insulatard Penfill 100 international units/ml||EU/1/02/233/006; EU/1/02/233/005; EU/1/02/233/007|
|Insulatard InnoLet 100 international units/ml||EU/1/02/233/011; EU/1/02/233/010; EU/1/02/233/012|
Novo Nordisk Limited
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+44 (0)1293 613535
+44 (0)1293 613555
+44 (0)845 600 5055
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