Summary of medicine characteristics - Ultratard
2. QUALITATIVE AND QUANTITATIVE COMPOSITION
Insulin human, rDNA (produced by recombinant DNA technology in Sacch
-
1 ml contains 40 IU of insulin human
1 vial contains 10 ml equivalent to 400 IU
One IU (International Unit) corresponds to 0.035 mg
aromyces c
Ultratard is an insulin zinc suspension. The suspension consists of crystalli
For excipients, see Section 6.1 List of excipients.
3. PHARMACEUTICAL FORM
Suspension for injection in a vial.
Treatment of diabetes mellitus.
Ultratard is a long-acting insulin.
4.1 Therapeutic indications
Ultratard is a cloudy, white, aqueous suspension.
4. CLINICAL PARTICULARS
4.2 Posology and method of admi
Dosage is individual and determined by the physician in accordance with the needs of the patient.
The average range of total daily insulin requirement for maintenance therapy in type 1 diabetic patients lies between 0.5 and 1.0 IU/kg. In pre-pubertal children it usually varies from 0.7to 1.0 IU/kg. During the period of partial remission, the insulin requirements can be much lower, whereas in insulin resistant states e.g. during puberty or due to obesity, the daily insulin requirement may be substantially higher.
Initial dosages for type 2 diabetic patients are often lower, e.g. 0.3 to 0.6 IU/kg/day.
The physician determines whether one or several daily injections are necessary. Ultratard 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.
In pr
ith diabetes mellitus optimised glycaemic control delays the onset and slows the of late diabetic complications. Blood glucose monitoring is therefore recommended.
Concomitant illness, especially infections and feverish conditions, usually increases the patient's insulin requirement.
Renal or hepatic impairment may reduce insulin requirement.
Adjustment of dosage may also be necessary if patients change physical activity or their usual diet. Dosage adjustment may be necessary when transferring patients from one insulin preparation to another (see section 4.4 Special warnings and special precautions for use).
all, the
For subcutaneous use.
Ultratard is usually administered subcutaneously in the thigh. If convenient, the a gluteal region or the deltoid region may also be used.
compared to the
Subcutaneous injection into the thigh results in a slower and less variable abs other injection sites.
Injection into a lifted skin fold minimises the risk of unintended intramuscular injection.
Keep the needle under the skin for at least 6 seconds to make sure the entire dose is injected. Injection sites should be rotated within an anatomic region in order to avoid lipodystrophy.
Insulin suspensions are never to be administered intravenously.
Ultratard is accompanied by a package leaflet with detailed instruction for use to be followed.
The vials are for use with insulin syringes with a correspo
unit scale.
4.3 Contraindications
4.3 ContraindicationsHypoglycaemia
Hypersensitivity to human insulin or to any of the excipients (see section 6.1 List of excipients).
4.4 Special warnings and special precautions for use
4.4 Special warnings and special precautions for useInadequate dosage or discontinuation of treatment, especially in type 1 diabetes, may lead to hyperglycaemia and diabetic ketoacidosis.
Usually the first symptoms of hyperglycaemia set in 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 (see section 4.8 Undesirable effects).
In type 1 diabetes, untreated hyperglycaemic events eventually lead to diabetic ketoacidosis, which is potentially lethal.
Hypoglycaemia may occur if the insulin dose is too high in relation to the insulin requirement.
Hypoglycaemia can generally be corrected by immediate carbohydrate intake. In order to be able to take action immediately, patients should carry glucose with them at all times.
Omission of a meal or unplanned, strenuous physical exercise may lead to hypoglycaemia.
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 (see section 4.8 Undesirable effects).
Usual warning symptoms may disappear in patients with longstanding diabetes.
Transferring a patient to another type or brand of insulin should be done under strict medical supervision. Changes in strength, brand (manufacturer), type (fast-, dual-, long-acting insulin etc.), species (animal, human or analogue insulin) and/or method of manufacture (recombinant DNA versus animal source insulin) may result in a change in dosage.
If an adjustment is needed when switching the patients to Ultratard, it may occur with the first dose or during the first several weeks or months.
A few patients who have experienced hypoglycaemic reactions after transfer from animal source insulin have reported that early warning symptoms of hypoglycaemia were less pronounced or different from those experienced with their previous insulin.
Before travelling between different time zones, the patient should be advised to consult the doctor,
since this may mean that the patient has to take insulin and meals at different times.
Insulin suspensions are not to be used in insulin infusion pumps.
Ultratard contains methyl parahydroxybenzoate, which may cause allergic reactions (possibly delayed).
4.5 Interaction with other medicinal products and other forms of interaction
4.5 Interaction with other medicinal products and other forms of interactionA number of medicinal products are known to interact with the glucose metabolism. The physician must therefore take possible interactions into account and should always ask their patients about any medicinal products they take.
Oral hypoglycaemic agents (OHA), monoamine oxidase inhibitors (MAOI), non-selective betablocking agents, angiotensin converting enzyme (ACE) inhibitors, salicylates and alcohol.
ics, growth hormone and
The following substances may increase insulin requirement: Thiazides, glucocorticoids, thyroid hormones and beta-sympath danazol.
Beta-blocking agents may mask the symptoms of hypoglycaemia and delay recovery from hypoglycaemia.
Octreotide/lanreotide may both decrease and increase insulin requirement.
ffect of insulin.
Alcohol may intensify and prolong the hypoglyc
4.6 Pregnancy and lactation
4.6 Pregnancy and lactations with insulin during pregnancy, as insulin does not
There are no restrictions on treatment o 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 control in the treatment of pregnant women with diabetes is therefore 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 return rapidly to pre-pregnancy values.
Insulin treatment of the nursing mother presents no risk to the baby. However, the Ultratard dosage may need to be adjusted.
4.7 Effect
lity to drive and use machines
ility to concentrate and react may be impaired as a result of hypoglycaemia. This may in situations where these abilities are of special importance (e.g. driving a car or operating machinery).
Patients should be advised to take precautions to avoid hypoglycaemia whilst 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.
4.8 Undesirable effects
4.8 Undesirable effectsThe most often seen undesirable effect in insulin-treated patients is a change in blood glucose levels. From clinical investigations it is known that major hypoglycaemia, defined as need for assistance in treatment, occurs in approximately 20% of well-controlled patients. Based on post-marketing experience adverse drug reactions including hypoglycaemia have been reported rarely (>1/10,000 <1/1,000). The listings below are all based on post-marketing experience and is subject to underreporting and should be interpreted in that light.
Metabolism and nutrition disorders
Rare
(>1/10,000 <1/1,000)
Change in blood glucose
Hypoglycaemia:
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. Severe hypoglycaemia may lead to unconsciousness and/or convulsions and may result in temporary or permanent impairment of brain function or even death.
Hyperglycaemia:
Usually the first symptoms of glycaemia set in gradually, over a period of hours or days. They e thirst, increased frequency of urination, nausea, vomiting, drowsiness, flushed dry skin, dry mouth, loss of appetite as well as acete odour of breath.
In type 1 diabetes, untreated hyperglycaemic events eventually lead to diabetic ketoacidosis is potentially lethal.
ion 4.4 Special warnings and special precautions
Eye disorders
Very rare (<1/10,000)
For precautions see for use.
Refraction anomalies may occur upon initiation of insulin therapy. These symptoms are usually of transitory nature.
General disorders and administration site conditions
Very rare (<1/10,000)
Very rar (<1/10,000)
Very rare (<1/10,000
Local hypersensitivity reactions (redness, swelling and itching at the injection site) may occur during treatment with insulin. These reactions are sually transitory and normally they disappear during continued treatment.
Lipodystrophy may occur at the injection site as a consequence of failure to rotate injection sites within an area.
Symptoms of generalised hypersensitivity may include generalised skin rash, itching, sweating, gastrointestinal upset, angioneurotic oedema, difficulties in breathing, palpitation and reduction in blood pressure. Generalised hypersensitivity reactions are potentially life threatening.
Very rare (<1/10,000)
Oedema may occur upon initiation of insulin therapy. These symptoms are usually of transitory nature.
4.9 Overdose
4.9 OverdoseA specific overdose of insulin cannot be defined. However, hypoglycaemia may develop over sequential stages:
- • Mild hypoglycaemic episodes can be treated by oral administration of glucose or sugary products. It is therefore recommended that the diabetic patient constantly carries some sugar lumps, sweets, biscuits or sugary fruit juice.
- • Severe hypoglycaemic episodes, where the patient has become unconscious, can be treated by glucagon (0.5 to 1 mg) given intramuscularly or subcutaneously by a person who has received appropriate instruction, or by glucose given intravenously by a medical professional. Glucose must also be given intravenously, if the patient does not respond to glucagon within 10 to 15 minutes.
Upon regaining consciousness, administration of oral carbohydrate is recommended for the patient in order to prevent relapse.
After an injection of glucagon, the patient should be monitored in a hospital in order to find the reason for this severe hypoglycaemia and prevent other similar episodes.
5. PHARMACOLOGICAL PROPERTIES5.1 Pharmacodynamic properties
Pharmacotherapeutic group: antidiabetic agent ATC code: A10A E01.
The 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.
Ultratard is a very long-acting insulin.
Onset of action is within 4 hours, reaches a maximum effect within 8–24 hours and the entire time of duration is approximately 28–32 hours.
5.2 Pharmacokinetic properties
5.2 Pharmacokinetic propertiesInsulin in the blood stream has a half-life of a few minutes. Consequently, the time-action profile of an insulin preparation is determined solely by its absorption characteristics.
This process is influenced by several factors (e.g. insulin dosage, injection route and site, thickness of subcutaneous fat, type of diabetes). The pharmacokinetics of insulins is therefore affected by significant intra- and inter-individual variation.
The maximum plasma concentration of the insulins is reached within 2–18 hours after subcutaneous administration.
No profound binding to plasma proteins, except circulating insulin antibodies (if present) has been observed.
Human 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.
The terminal half-life is determined by the rate of absorption from the subcutaneous tissue. The terminal half-life (t/2) 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 t/2 of a few minutes). Trials have indicated a t/2 of about 13–15 hours.
5.3 Preclinical safety datagradation of the insulin, e.g. if the
Preclinical data reveal no special hazard for humans based on conventional studies of safe pharmacology, repeated dose toxicity, genotoxicity, carcinogenic potential, toxicity to rep
6. PHARMACEUTICAL PARTICULARS6.1 List of excipients
Zinc chloride
Sodium chloride
Methyl parahydroxybenzoate
Sodium acetate
Sodium hydroxide or/and hydrochloric acid (for pH adjustment)
Water for injections
6.2 Incompatibilities
Insulin suspensions should not be added to infusion fluids. Medicinal products added to the insulin suspension may ca medicinal products contain thiols or sulphites.
ns is not recommended due to the risk of
Mixing of Ultratard with phosphate buffered insulin prepa precipitation of zinc-phosphate, leading to an unpredictable timing of such insulin mixtures. When mixing Actrapidwith Ultratard immediate injection is necessary to avoid blunting of the fast acting effect of Actrapid.
6.3 Shelf life
6.3 Shelf lifeAfter first opening: 6 weeks.
6.4 Special precautions for st
6.5 Nature and contents of container ♦ VJ
7. MARKETING AUTHORISATION HOLDER
Novo Nordisk A/S
Novo Allé
DK-2880 Bagsværd
Denmark
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