HUMULIN N (NPH)
= Additional active ingredients
NPH Human insulin (recombinant DNA origin), isophane suspension. An intermed. acting insulin with a slower onset of action than that of regular insulin and a longer duration of activity (slightly less than 24 hrs.).
PRESENTATION AND DOSSAGE
CARTRIDGE: 5 x 3.0 ml x 100 I.U./ ml.
VIALS: 10 ml x 100 U/ml.
Hypersensitivity to Humulin or to the formulation excipients, unless used as part of a desensitisation programme.
Under no circumstances should any Humulin formulation other than Humulin Soluble be given intravenously.
Transferring a patient to another type or brand of insulin should be done under strict medical supervision. Changes in strength, brand (manufacturer), type (soluble, isophane, mixture, etc.), species (animal, human, human insulin analogue), and/or method of manufacture (recombinant DNA versus animal-source insulin) may result in the need for a change in dosage. Some patients taking human insulin may require a change in dosage from that used with animal-source insulins. If an adjustment is needed, it may occur with the first dose or during the first several weeks or months.
A few patients who experienced hypoglycaemic reactions after transfer to human insulin have reported that the early warning symptoms were less pronounced or different from those experienced with their previous animal insulin. Patients whose blood glucose is greatly improved, e.g. by intensified insulin therapy, may lose some or all of the warning symptoms of hypoglycaemia and should be advised accordingly. Other conditions which may make the early warning symptoms of hypoglycaemia different or less pronounced include long duration of diabetes, diabetic nerve disease, or medications such as beta blockers. Uncorrected hypoglycaemic and hyperglycaemic reactions can cause loss of consciousness, coma or death. The use of dosages which are inadequate or discontinuation of treatment, especially in insulin-dependent diabetics, may lead to hyperglycaemia and diabetic ketoacidosis; conditions which are potentially lethal. Treatment with human insulin may cause formation of antibodies, but titres of antibodies are lower than those to purified animal insulin. Insulin requirements may change significantly in diseases of the adrenal, pituitary or thyroid glands and in the presence of renal or hepatic impairment. Insulin requirements may be increased during illness or emotional disturbances. Adjustment of insulin dosage may also be necessary if patients change their level of physical activity or change their usual diet.
Hypoglycaemia is the most frequent undesirable effect of insulin therapy that a patient with diabetes may suffer. Severe hypoglycaemia may lead to loss of consciousness, and in extreme cases, death. No specific frequency for hypoglycaemia is presented, since hypoglycaemia is a result of both the insulin dose and other factors e.g. a patient`s level of diet and exercise. Local allergy in patients is common (1/100 to < 1/10). Redness, swelling, and itching can occur at the site of insulin injection. This condition usually resolves in a few days to a few weeks. In some instances, local reactions may be related to factors other than insulin, such as irritants in the skin cleansing agent or poor injection technique.
Systemic allergy, which is very rare (< 1/10,000) but potentially more serious, is a generalised allergy to insulin. It may cause rash over the whole body, shortness of breath, wheezing, reduction in blood pressure, fast pulse, or sweating. Severe cases of generalised allergy may be life-threatening. In the rare event of a severe allergy to Humulin, treatment is required immediately. A change of insulin or desensitisation may be required. Lipodystrophy at the injection site is uncommon (1/1,000 to < 1/100). Cases of edema have been reported with insulin therapy, particularly if previous poor metabolic control is improved by intensified insulin therapy.
A number of medicinal products are known to interact with glucose metabolism and therefore the physician should be consulted when using other medications in addition to human insulin. The physician must therefore take possible interactions into account and should always ask his patients about any medicinal products they take.
Insulin requirements may be increased by substances with hyperglycaemic activity, such as, glucocorticoids, thyroid hormones, growth hormone, danazol, beta2-sympatomimetics (such as ritodrine, salbutamol, terbutaline) and thiazides.
Insulin requirements may be reduced in the presence of substances with hypoglycaemic activity, such as oral hypoglycaemics (OHA), salicylates (for example, acetylsalicylic acid), certain antidepressants (monoamine oxidase inhibitors), certain angiotensin converting enzyme (ACE) inhibitors (captopril, enalapril), angiotensin II receptor blockers, non-selective beta-blocking agents and alcohol. Somatostatin analogues (octreotide, lanreotide) may both decrease or increase insulin dose requirements.
The dosage should be determined by the physician, according to the requirement of the patient.
Humulin Soluble should be given by subcutaneous injection but may, although not recommended, also be given by intramuscular injection. It may also be administered intravenously. Humulin Isophane and Mixtures in vials and Humulin Isophane and Mixtures in cartridge presentations should be given by subcutaneous injection but may, although not recommended, also be given by intramuscular injection. These formulations should not be administered intravenously.
Subcutaneous administration should be in the upper arms, thighs, buttocks or abdomen. Use of injection sites should be rotated so that the same site is not used more than approximately once a month. Care should be taken when injecting any Humulin insulin preparations to ensure that a blood vessel has not been entered. After any insulin injection, the injection site should not be massaged. Patients must be educated to use proper injection techniques. Humulin Isophane may be administered in combination with Humulin Soluble. (See Section 6.6 Instructions for use / handling – for Mixing of Insulins). Humulin Mixture formulations are ready-made defined mixtures of Humulin Soluble and Humulin Isophane insulin designed to avoid the need for the patient to mix insulin preparations. A patient’s treatment regimen should be based on their individual metabolic requirements. Each pack contains a patient information leaflet with instructions on how to inject insulin.
Insulin has no specific overdose definitions, because serum glucose concentrations are a result of complex interactions between insulin levels, glucose availability and other metabolic processes. Hypoglycaemia may occur as a result of an excess of insulin relative to food intake and energy expenditure. Hypoglycaemia may be associated with listlessness, confusion, palpitations, headache, sweating and vomiting. Mild hypoglycaemic episodes will respond to oral administration of glucose or sugar products. Correction of moderately severe hypoglycaemia can be accomplished by intramuscular or subcutaneous administration of glucagon, followed by oral carbohydrate when the patient
recovers sufficiently. Patients who fail to respond to glucagon must be given glucose solution intravenously.
If the patient is comatose, glucagon should be administered intramuscularly or subcutaneously. However, glucose solution must be given intravenously, if glucagon is not available or if the patient fails to respond to glucagon. The patient should be given a meal as soon as consciousness is recovered. Sustained carbohydrate intake and observation may be necessary because hypoglycaemia may occur after apparent clinical recovery.
PREGNANCY & LACTATION
It is essential to maintain good control of the insulin treated (insulin-dependent or gestational diabetes) patient throughout pregnancy. Insulin requirements usually fall during the first trimester and increase during the second and third trimesters. Patients with diabetes should be advised to inform their doctors if they are pregnant or are contemplating pregnancy. Careful monitoring of glucose control, as well as general health, is essential in pregnant patients with diabetes.Patients with diabetes who are lactating may require adjustments in insulin dose and/or diet.
MANUFACTURER & DISTRIBUTER:
Manufacturer: Eli Lilly Israel Ltd.