INFORMATION FOR HEALTH PROFESSIONALS
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Velosulin HM(ge) is a sterile, clear, colourless, aqueous solution of insulin human. One IU (International Unit) corresponds to 0.035 mg of anhydrous human insulin.
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.
Insulin 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) which is why considerable intra- and inter-patient variations are seen.
For Velosulin® HM(ge) the fast absorption is due to the product being a solution.
Continuous subcutaneous infusion eliminates some of the variations/fluctuations inherent to injection therapy.
The relatively fast absorption of soluble insulin ensures a constant supply of insulin to the blood from a relatively small pool under the skin.
An average action profile after subcutaneous injection indicates:
Onset: within ½ hour
Maximum: between 1 and 3 hours
Duration: approximately 8 hours
Treatment of diabetes mellitus. Furthermore indicated for the initial stabilisation of diabetes, during treatment of diabetic ketoacidosis and the hyperosmolar non ketotic syndrome, and during stress situations such as severe infections and major surgery in diabetic patients.
This phosphate-buffered soluble insulin is intended for continuous subcutaneous insulin infusion (CSII) in external insulin infusion pumps. Only syringes made of polyethylene, polypropylene or glass are recommended. The only catheters recommended are those where the material in contact with the insulin is made of polyethylene or polypropylene. Likewise the only needles recommended are teflon coated or stainless steel needles.
Patients started on CSII must receive comprehensive instruction in the use of the pump, and the necessary actions in case of illness, hypoglycaemia, hyperglycaemia or pump failure.
Dosage is individual and determined by the physician in accordance with the needs of the patient. Usually, 40-60% of the total daily dose is given as a continuous basal rate and the remaining 40-60% as boluses divided between the three main meals.
In general, when patients are transferred from injection to infusion therapy, it may be advisable to reduce the dosage by initiating the patient at 90% of the previous total daily dosage, with 40% as basal rate and 50% as boluses divided between the three main meals.
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. However, in pre-pubertal children it usually varies from 0.7 to 1.0 IU/kg, but can be much lower during the period of partial remission. In insulin resistance, 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.
In patients with diabetes mellitus optimised metabolic control delays the onset and slows the progression of late diabetic complications. Optimised metabolic control, including glucose monitoring, is therefore recommended.
In geriatric patients the primary aim of treatment may be symptom relief and avoidance of hypoglycaemic events.
Velosulin HM(ge) is intended for administration by CSII, usually in the abdominal wall.
Administration of Velosulin HM(ge) is also possible by subcutaneous, intramuscular or intravenous injection. Subcutaneous injection is usually done in the abdominal wall, although the thigh, the gluteal region or the deltoid region may also be used. Injection into a lifted skin fold minimises the risk of intramuscular injection. When combination with intermediate or long acting insulin is necessary it is only possible to mix Velosulin HM(ge) with isophane or premixed insulins.
Intramuscular administration should only be performed under the guidance of a physician.
Intravenous administration should only be carried out by a physician.
In order to avoid lipodystrophy, injection sites for a given insulin preparation should be rotated within an anatomic region.
Patients administering Velosulin HM(ge) by CSII must have injection syringes and alternative insulin readily available in case of emergency or pump interruption or failure, in order that insulin can be administered by subcutaneous injection.
A CSII bolus or a bolus injection should be followed by a meal or snack containing carbohydrates within 30 minutes.
Hypoglycaemia.
Hypersensitivity to human insulin or any of the excipients.
Inadequate 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 the breath.
In type 1 diabetes, untreated hyperglycaemic events eventually lead to diabetic ketoacidosis which is potentially lethal.
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 increase their physical activities or change their usual diet.
Transferring a patient to another type or brand of insulin should be done under strict medical supervision. Changes in strength, brand (manufacturer), type (rapid acting insulin, intermediate acting insulin, long acting insulin etc.), species (animal, human insulin analog) and/or method of manufacturer (recombinant DNA versus animal source insulin) may result in the need for a change in dose.
Patients switching to Velosulin® HM(ge) may require a change in their usual insulin dosage.
If an adjustment is needed, 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.
Patients whose blood glucose control has greatly improved e.g. by intensified insulin therapy, may experience a change in their usual warning symptoms of hypoglycaemia and should be advised accordingly.
When administered by CSII Velosulin® HM(ge) should never be mixed with any other insulin.
Velosulin HM(ge) should not be mixed with insulin zinc suspensions since the phosphate buffer can interact with the zinc in the suspensions and alter the timing of action of the mixture in an unpredictable way.
There are no restrictions on the treatment of diabetes with insulin during pregnancy as insulin does not pass the placental barrier. Intensified control in the treatment of pregnant women with diabetes is 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 return rapidly to pre-pregnancy values.
There are no restrictions on the treatment of diabetes with insulin during lactation, as insulin treatment of the nursing mother involves no risk to the baby. However, the insulin dosage may need to be reduced.
The patient's 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 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.
Hypoglycaemia is a frequently occurring undesirable effect of insulin therapy. Symptoms of hypoglycaemia usually occur suddenly. They may include cold sweat, cool pale skin, nervousness or tremor, anxious feeling, unusual tiredness or weakness, confusion, difficulty in concentration, drowsiness, excessive hunger, temporary vision changes, headache, nausea and palpitation. Severe hypoglycaemia may lead to unconsciousness and may result in temporary or permanent impairment of brain function or even death.
Oedema and refraction anomalies may occur upon initiation of insulin therapy. These symptoms are usually of transitory nature.
Local hypersensitivity reactions (redness, swelling and itching at the injection site) may occur during treatment with insulin. These reactions are usually transitory and normally they disappear during continued treatment.
Generalised hypersensitivity reactions may occasionally occur. They are potentially more serious and may cause 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.
Lipodystrophy may occur at the injection site as a consequence of failure to rotate injection site within an area.
Patients using CSII may be more prone to infection at the site of infusion. Infections can be minimised by careful attention to personal hygiene of the hands and infusion site and by frequent changes of catheter (maximum usage 2 days).
A number of drugs are known to interact with the glucose metabolism. Possible interactions must therefore be taken into account by the physician.
The following substances may reduce the insulin requirements:
Oral hypoglycaemic agents (OHA), octreotide, monoamine oxidase inhibitors (MAOI), non-selective beta-blocking agents, angiotensin converting enzyme (ACE) inhibitors, salicylates, alcohol and anabolic steroids.
The following substances may increase the insulin requirements:
Oral contraceptives, thiazides, glucocorticoids, thyroid hormones and sympathomimetics, danazol.
Beta-blocking agents may mask the symptoms of hypoglycaemia. Alcohol may intensify and prolong the hypoglycaemic effect of insulin.
There are no specific overdose definitions for insulins.
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 carry 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 glucose given intravenously by a medical professional. Glucose must also be given i.v. 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.
Vial of 10 ml made of glass. The vial is closed with a rubber closure and packed in a carton.
The carton contains a package leaflet with instructions for use and handling.
In general terms, insulin should only be added to compounds with which it has known compatibility. Drugs added to the insulin solution may cause degradation of the insulin, e.g. if the drugs contain thiols or sulphites. Upon mixing Velosulin® HM(ge) with infusion fluids an unpredictable amount of insulin will be adsorbed to the infusion material. Monitoring of the patient's blood glucose during infusion is therefore recommended.
When administered by CSII no other drugs or other insulins should be mixed in the reservoir of the infusion pump with Velosulin® HM(ge).
Velosulin® HM(ge) may be used/kept in the pump reservoir for six days close to the body.
Insulin preparations should be stored at 2°C - 8°C (in a refrigerator in the original container); not in or near the freezing compartment. Insulin preparations which have been frozen must not be used.
Insulin preparations should be protected from excessive heat and sunlight.
Insulin solutions should not be used if they do not appear water-clear and colourless.
Prescription Medicine
Vial of 10 ml.
Pre-clinical tests in various species have been performed and none of these resulted in unexpected, remarkable findings.
Glycerol
Metacresol
Zinc chloride
Disodium phosphate dihydrate
Sodium hydroxide
Hydrochloric acid
Water for injections
Novo Nordisk Pharmaceuticals Ltd.
PO Box 51-268
Pakuranga
Auckland
Tel: (09) 579 0653
Fax: (09) 579 0654
28 December 2002
Velosulin is a trade name owned by Novo Nordisk A/S, Denmark