Novolin (Insulin)

NOVOLIN®GE Preparations

Novo Nordisk

Insulin Human (Biosynthetic)

Antidiabetic Agent

Action And Clinical Pharmacology: Novolin®ge Biosynthetic Human Insulin is a polypeptide structurally identical to natural human insulin.

Novolin®ge is produced by recombinant DNA technology, using Saccharomyces cerevisiae (baker’s yeast). The content of immunoreactive peptides derived from the used microorganism (yeast) is undetectable (less than 1 ppm by weight of the dry insulin) as determined by enzyme linked immunoabsorbent assay.

When administered in appropriate regular doses to patients with diabetes mellitus and who follow a controlled diet and exercise program, Novolin®ge temporarily restores their ability to metabolize carbohydrates, protein and fats.

The Novolin®ge insulin formulations differ with respect to onset, peak and duration of action. These times reflect averages and can vary depending upon the individual patient

Novolin®ge Toronto, (Insulin Injection, Human Biosynthetic) is a clear, colorless neutral solution of human insulin with a short duration of action. The effect of Novolin®ge Toronto after s.c. administration begins after approximately 0.5 hours, is maximal between 2.5 and 5 hours and terminates after approximately 8 hours.

Novolin®ge NPH (Insulin Isophane, Human Biosynthetic) is a cloudy neutral suspension of human isophane insulin with an intermediate duration of action. The effect of Novolin®ge NPH begins after approximately 1.5 hours, is maximal between 4 and 12 hours and terminates after approximately 24 hours.

Novolin®ge Lente (Insulin Zinc Suspension-Medium, Human Biosynthetic) is a cloudy neutral suspension of human insulin with an intermediate duration of action. Thirty percent (30%) of the insulin is present in amorphous form and 70% in crystalline form. The effect of Novolin®ge Lente begins after approximately 2.5 hours, is maximal between 7 and 15 hours and terminates after approximately 22 hours.

Novolin®ge Ultralente (Insulin Zinc Suspension – Prolonged, Human Biosynthetic) is a cloudy neutral suspension of human insulin with a prolonged duration of action. The insulin is present in crystalline form. The effect of Novolin®ge Ultralente begins after approximately 4 hours, is maximal between 8 and 24 hours and terminates after approximately 28 hours.

Novolin®ge Premixed Insulin Preparations: Novolin®ge 10/90, Novolin®ge 20/80, Novolin®ge 30/70, Novolin®ge 40/60, Novolin®ge 50/50: These are a series of premixed insulins containing various proportions of Novolin®ge Toronto and Novolin®ge NPH, respectively, in the proportions indicated by the ratio in the product name. The mixtures are cloudy, neutral suspensions with an intermediate duration of action. The strength of the initial effect is dependent on the amount of Novolin®ge Toronto in the mixture. The effect of Novolin®ge mixtures begins after approximately 0.5 hours, is maximal between 2 and about 12 hours and terminates after approximately 24 hours.

Novolin®ge Lente, Novolin®ge NPH or Novolin®ge Ultralente may be mixed with Novolin®ge Toronto in order to meet the requirements of individual patients with diabetes as determined by the physician.

Indications And Clinical Uses: For the treatment of insulin-requiring patients with diabetes.

Only Novolin®ge Toronto, using i.v. administration, should be used for the treatment of emergencies, such as diabetic coma and pre-coma, and in patients with diabetes undergoing surgery. See also Contraindications.

Contra-Indications: Insulin is contraindicated in hypoglycemia (see Hypoglycemia and Overdose: Treatment).

Novolin®ge Lente, Novolin®ge Ultralente, Novolin®ge NPH and Novolin®ge premixed insulin preparations should not be administered i.v. or i.m., nor are they suitable for the treatment of diabetic coma.

Manufacturers’ Warnings In Clinical States: Novolin®ge Toronto should not be used if it is not water-clear and colorless. Due to the risk of precipitation in some pump catheters, Novolin®ge Toronto is not recommended for use in insulin pumps.

Novolin®ge Lente, Novolin®ge Ultralente, Novolin®ge NPH and Novolin®ge premixed insulin suspensions should not be used if the precipitate has become lumpy or granular in appearance or has formed a deposit of solid particles on the wall of the vial or cartridge. These insulin suspensions should also not be used if the contents remain clear after the vial or cartridge has been shaken carefully.

To avoid possible transmission of disease, a Penfill® cartridge must not be used by more than 1 person.

A few patients have reported that after being transferred to human insulin, the early warning symptoms for hypoglycemia were less pronounced than they were with animal-source insulin. Such patients should frequently measure their blood glucose and consult their doctor for dose adjustments, if necessary.

Insulin should not be used after the expiration date printed on the package.

Novolin®ge in vials: A U-100 syringe should always be used. Failure to use the correct syringe can lead to dosage errors.

Insulin should only be mixed as directed by the physician. Novolin®ge Toronto should only be mixed in the syringe with insulins of equal purity (eg., Novolin®ge Lente, Novolin®ge NPH or Novolin®ge Ultralente). The order of mixing and brand or model of syringe should be specified by the physician. In general when longer-acting insulins are mixed with short-acting soluble insulins, the short-acting insulin should be drawn into the syringe first. When mixing regular insulin with insulin zinc suspensions, the insulin mixture should be injected immediately.

Novolin®ge Penfill® cartridges are designed only for use in Novolin-Pen® systems. If treatment involves 2 insulins in Penfill® cartridges, a separate Novolin-Pen® system should be used for each type of insulin.

Novolin®ge Penfill® must not be refilled.

Use only Novolin®ge Penfill® cartridges and NovoFine® needles with Novolin-Pen® systems. NovoFine® needles should be removed after each injection. If the needle is not removed, changes in ambient temperature can result in some liquid being expelled from the cartridge. In the case of insulin suspensions, removal of supernatant liquid can cause an increase in insulin concentration (i.e. strength) within the cartridge.

Precautions: Stress or illness may increase insulin requirements. In these instances, patients should contact their physician and carefully control and monitor their blood glucose. The concomitant use of corticosteroids, oral contraceptives, diuretics, tricyclic antidepressants and the initiation of thyroid hormone replacement therapy may lead to an increase in insulin requirements. If a beta-adrenergic blocking agent or a MAO inhibitor is added to the patient’s treatment, adjustment of the insulin dosage may be necessary.

An insulin reaction (hypoglycemia) may occur if the patient takes too much insulin, misses meals or exercises more than usual (see Hypoglycemia and Overdose: Treatment).

Patients with diabetes should be instructed to carry a few lumps of sugar, candies or biscuits to prevent the progression of a hypoglycemic reaction, should one occur. The patient with diabetes should make relatives and close work-mates aware that he/she is diabetic and instruct them regarding signs and symptoms of hypoglycemia and assistance in the event of a hypoglycemic reaction. An unconscious person should not be given anything to eat or drink as choking is possible.

Diabetic ketosis, ketoacidosis or coma may develop if patient takes less insulin than needed. This could be due to increased insulin demand during illness or infection, neglect of diet, omission or maladministration of prescribed insulin doses. A developing ketoacidosis will be revealed by urine tests which show large amounts of sugar and acetone. The symptoms of thirst, large urine volumes, loss of appetite, fatigue, dry skin and deep and rapid breathing come on gradually, usually over a period of some hours or days. If hyperglycemia is not treated, it can cause diabetic coma or death.

Pregnancy and Lactation: During pregnancy and lactation, diabetes may become more difficult to manage. On the other hand, optimal metabolic control not only during pregnancy, but also prior to conception has proven to be beneficial in reducing the risk of miscarriage and malformation of the fetus. Patients with diabetes who have become pregnant or desire to become pregnant should consult their doctor for advice. Insulin ingested with the mother’s milk has not been associated with any risk for the baby.

Adverse Reactions: At initiation of insulin therapy, edema and refraction anomalies may occur. These conditions are usually of a transitory nature.

Occasionally, transitory redness, swelling, and itching at the injection site can either be caused by the insulin as such or the preservative used in the preparation. These reactions will often be of a non-specific and transitory nature. In very rare cases lipoatrophy or lipohypertrophy can develop at the injection site. Patients should change the injection site to avoid this side effect.

If, in exceptional cases, redness at the injection site quickly spreads as rash and blisters over the whole body, immediate medical attention is required. This is extremely rare with the use of Novolin®ge (Insulin, Human Biosynthetic).

Hypoglycemia

In rare cases, the nature and intensity of hypoglycemia warning symptoms may change. This has been observed in patients with long duration of diabetes (with diabetic neuropathy), after changes of regimen and in patients on strict metabolic control. However, if severe hypoglycemia is not treated it may cause temporary or permanent brain damage or death.

A few patients have reported that after being transferred to human insulin, the early warning symptoms for hypoglycemia were less pronounced than they were with animal-source insulin. Such patients should frequently measure their blood glucose and consult their doctor for dose adjustment, if necessary.

In the event of an overdose, if the patient is conscious, glucose should be given orally. Where the patient is unconscious, an i.m, s.c. or i.v. injection of glucagon should be given and oral carbohydrate administered when the patient responds. Alternatively i.v. glucose may be administered; it must be given if there is no response to glucagon.

Dosage And Administration: Novolin®ge is made in one strength, 100 units/mL. The dosage is determined by the physician in accordance with the needs of the patient.

Novolin®ge Toronto when used alone is usually given 3 or more times daily. Novolin®ge Toronto may also be used in combination with longer-acting insulins of equal purity to suit the needs of the individual patients. It may be given s.c., i.m. or i.v. The s.c. injection of Novolin®ge Toronto should be followed by a meal within approximately 30 minutes of administration.

Novolin®ge Lente may be given once daily or more usually twice daily. It is administered by s.c. injection.

Novolin®ge Ultralente is usually given once daily, often in the evening. It is administered by s.c. injection.

Novolin®ge NPH is usually given once or twice daily. It is administered by s.c. injection.

Novolin®ge Premixed Insulin Preparations: Novolin®ge 10/90, Novolin®ge 20/80, Novolin®ge 30/70, Novolin®ge 40/60, Novolin®ge 50/50 are usually given once or twice daily, especially when a strong initial effect is desired. They are administered by s.c. injection. The injection of Novolin®ge premixed insulins should be followed by a meal within approximately 30 minutes of administration.

Insulin suspensions should be carefully shaken to ensure that the contents are uniformly mixed before injection of each dose.

Mixing Insulin: In vitro studies demonstrate an interaction occurs when zinc from Lente preparations (i.e., Novolin®ge Lente and Novolin®ge Ultralente) is mixed with insulin injection such as Novolin®ge Toronto. This binding may result in a blunting of the timing of onset of the Novolin®ge Toronto. The degree of interaction has been shown to be dependent on the ratio of regular to longer acting insulin and on the time between mixing and injection. However, when mixing Novolin®ge Toronto and Novolin®ge NPH the blunting effect is not observed and the rapid onset of Novolin®ge Toronto is preserved.

Novolin-Pen® systems are insulin delivery devices for use with Novolin®ge Penfill® insulin cartridges and NovoFine® needles. Novolin-Pen® 3 has a dial-a-dose selector which allows delivery of 2 to 70 units of insulin in increments of 1 unit from a 3 mL Penfill® cartridge. Novolin-Pen® 1.5 has a dial-a-dose selector which allows 2 to 40 units of insulin to be delivered in increments of 1 unit from a 1.5 mL Penfill® cartridge.

The following are general prescribing guidelines: New Patients: Although each patient must be assessed individually, initial stabilization on multiple injections of Novolin®ge Toronto is recommended. Following this, most patients will respond well to a regimen of Novolin®ge Lente twice daily; Novolin®ge NPH once or twice daily; or Novolin®ge Ultralente once daily. Usually small amounts of Novolin®ge Toronto are added to cover the morning and evening meals. Alternatively, Novolin®ge premixed insulin preparations may be given once or twice daily.

Transfer of Patients: When patients are transferred from other insulins to Novolin®ge , the change should be made as directed by the physician according to the following general guidelines:

When a switch is made from mixed species (porcine/bovine) or bovine insulin to human insulin a dosage adjustment may be required dependent upon dosage, purity, species and formulation of the insulin(s) currently administered. Variations in glycemic control may occur and adjustments in therapy should be made under the guidance of a physician. For patients currently controlled on porcine monocomponent or other highly purified human or porcine insulins, no dosage change is anticipated other than the routine adjustments made in order to maintain stable diabetic control.

Patients currently on self-prepared mixtures may be transferred to the closest available Novolin®ge fixed mixture preparation.

Any patient on a total daily dose of greater than 100 units of insulin may need to be closely monitored by the physician when transferring to a different insulin preparation, preferably in hospital.

Availability And Storage: Vials of 10 mL. Insulin cartridges of 1.5 and 3 mL. All in a strength of 100 units/mL. Novolin®ge preparations are available in the following presentations.

Storage: Insulin preparations including Penfill® cartridges should be stored between 2 and 10°C. They should not be exposed to heat or sunlight, and should never be frozen.

A vial in use can be kept at room temperature (max. 25°C) for 1 month. Novolin®ge Penfill® when used in Novolin-Pen® systems can be in-use or carried as a spare for up to 1 month at ambient temperature (max. 37°C). When in use, Novo Nordisk injection devices and their cartridges should not be refrigerated.

Insulin should not be used after the expiry date printed on the package.

Novo Nordisk cannot be held responsible for malfunctions occurring as a consequence of using Novo Nordisk insulin or insulin delivery systems in combination with products that do not meet Novo Nordisk specifications or quality standards.

NOVOLIN®GE Preparations Novo Nordisk Insulin Human (Biosynthetic) Antidiabetic Agent

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