HUMULIN N KWIKPEN Insulin Human (rDNA) 100IU / mL Suspension for SC Injection 3mL 5's

Indications/Uses

For the treatment of patients with diabetes mellitus who require insulin for the maintenance of glucose homeostasis.

Dosage/Direction for Use

The dosage should be determined by the physician, according to the requirement of the patient.
Insulin Human (Humulin N) should be given by subcutaneous injection. This formulation 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.
Vial: Pediatric population: No data are available.
Insulin Human (rDNA) (Humulin N) may be administered in combination with Insulin Human (rDNA) (Humulin R). (See Instructions for use and handling for Mixing of Insulins under Cautions for Usage).

Overdosage

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. Hypoglycemia may occur as a result of an excess of insulin relative to food intake and energy expenditure.
Hypoglycemia may be associated with listlessness, confusion, palpitations, headache, sweating and vomiting.
Mild hypoglycemic episodes will respond to oral administration of glucose or sugar products.
Correction of moderately severe hypoglycemia 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 hypoglycemia may occur after apparent clinical recovery.

Contraindications

Hypoglycemia.
Hypersensitivity to Humulin or to the formulation excipients, unless used as part of a desensitization program.
Under no circumstances should any Humulin formulation, other than Humulin R (Soluble), be given intravenously.

Special Precautions

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), 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 hypoglycemic 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 hypoglycemia and should be advised accordingly. Other conditions which may make the early warning symptoms of hypoglycemia different or less pronounced include long duration of diabetes, diabetic nerve disease, medications such as beta-blockers. Uncorrected hypoglycemic and hyperglycemic 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 hyperglycemia and diabetic ketoacidosis, conditions which are potentially lethal.
Treatment with human insulin may cause formation of antibodies, but titers 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.
Combination of human insulin with pioglitazone: Cases 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 human insulin is considered. If the combination is used, patients should be observed for signs and symptoms of heart failure, weight gain and edema. Pioglitazone should be discontinued, if any deterioration in cardiac symptoms occurs.
Excipients: Vial: This medicinal product contains less than 1 mmol sodium (23 mg) per dose, i.e., essentially "sodium‑free".
Effects on ability to drive and use machines: The patient's ability to concentrate and react may be impaired as a result of hypoglycemia. 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 hypoglycemia whilst driving, this is particularly important in those who have reduced or absent awareness of the warning signs of hypoglycemia or have frequent episodes of hypoglycemia. The advisability of driving should be considered in these circumstances.

Use In 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.

Adverse Reactions

Hypoglycemia is the most frequent undesirable effect of insulin therapy that a patient with diabetes may suffer. Severe hypoglycemia may lead to loss of consciousness, and in extreme cases, death. No specific frequency for hypoglycemia is presented, since hypoglycemia 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 generalized 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 generalized allergy may be life-threatening. In the rare event of a severe allergy to Insulin Human (Humulin N), treatment is required immediately. A change of insulin or desensitization 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 (see Precautions).
Reporting of suspected adverse reactions: Reporting suspected adverse reactions after authorization 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.

Drug Interactions

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 (see Precautions). The physician must therefore take possible interactions into account and should always ask his patients about any medicinal products they take.
Cartridge and Vial: Insulin requirements may be increased by substances with hyperglycemic activity, such as glucocorticoids, thyroid hormones, growth hormone, danazol, beta2-sympathomimetics (such as ritodrine, salbutamol, terbutaline), thiazides.
Vial and KwikPen: Insulin requirements may be reduced in the presence of substances with hypoglycemic activity, such as oral hypoglycemics (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.

Caution For Usage

Incompatibilities: Insulin Human (Humulin N) preparations should not be mixed with insulins produced by other manufacturers or with animal insulin preparations.
Special precautions for disposal and other handling: Do not reuse needles. Dispose of the needle in a responsible manner. Needles and pens must not be shared. Cartridges/prefilled pens (KwikPen)/vials can be used until empty, then properly discard. Any unused product or waste material should be disposed of in accordance with local requirements.
Cartridge: Lilly 3 mL cartridges are designed and tested for use with Lilly pens.
Instructions for use and handling: Cartridges: a) Preparing a dose: Cartridges containing Insulin Human (Humulin) formulation should be rolled in the palms of the hands ten times and inverted 180° ten times immediately before use to resuspend the insulin until it appears uniform cloudy or milky. If not, repeat the previous procedure until contents are mixed. Cartridges contain a small glass bead to assist mixing. Do not shake vigorously as this may cause frothing, which may interfere with the correct measurement of the dose.
The cartridges should be examined frequently and should not be used if clumps of material are present or if solid white particles stick to the bottom or wall of the cartridge, giving a frosted appearance.
The cartridges are not designed to allow any other insulin to be mixed in the cartridge. Cartridges are not designed to be refilled.
b) Injecting a dose: Inject the correct dose of insulin, as directed by the doctor or diabetes specialist nurse.
Vial: A suspension for injection in a 10mL vial to be used in conjunction with an appropriate syringe (100 IU/mL markings).
a) Preparing a dose: Vials containing Insulin Human (rDNA) (Humulin N) formulation should be rotated several times in the palms of the hands before use to completely resuspend the insulin, until it appears uniformly cloudy or milky. If not, repeat the previous procedure until contents are mixed.
Do not shake vigorously as this may cause frothing, which may interfere with the correct measurement of the dose.
The vials should be examined frequently and should not be used if clumps of material are present or if solid white particles stick to the bottom or wall of the vial, giving a frosted appearance.
Mixing of insulins: The shorter acting insulin should be drawn into the syringe first, to prevent contamination of the vial by the longer acting preparation. It is advisable to inject directly after mixing. However, if a delay is necessary, a consistent routine must be followed.
Alternatively, a separate syringe or, separate cartridges of Insulin Human (rDNA) (Humulin R) and Insulin Human (rDNA) (Humulin N), can be used for administration of the correct amount of each formulation.
Prepare the syringe prior to injection, as directed by the doctor or diabetes specialist nurse.
Use an insulin syringe marked for the strength of insulin being administered.
b) Injecting a dose: Inject the correct dose of insulin, as directed by the doctor or diabetes specialist nurse. Use of the injection sites should be rotated so that the same is not used more than approximately once a month.
KwikPen: A suspension for injection in a prefilled pen injector containing 3 mL cartridge. Insulin Human (Humulin N KwikPen) delivers up to 60 units per dose in single increments.
a) Preparing a dose: Insulin Human (Humulin N KwikPen) formulation should be rolled in the palms of the hands ten times and inverted 180° ten times immediately before use to resuspend the insulin until it appears uniform cloudy and milky. If not, repeat the previous procedure until contents are mixed. Cartridges contain a small glass bead to assist mixing. Do not shake vigorously as this may cause frothing, which may interfere with the correct measurement of the dose.
The cartridges should be examined frequently and should not be used if clumps of material are present or if solid white particles stick to bottom or wall of the cartridge, giving a frosted appearance.
Follow the instructions with Insulin Human (Humulin N KwikPen) for attaching the needle and administering the insulin injection.
Insulin Human (Humulin N KwikPen) a needle must always be attached before priming dialing and injecting an insulin dose. It should always be primed before each injection. Failure to prime Insulin Human (Humulin N KwikPen) may result in an inaccurate dose.
b) Injecting a dose: Inject the correct dose of insulin, as directed by the doctor or diabetes specialist nurse. Use of the injection sites should be rotated so that the same site is not used more than approximately once a month.

Storage

Cartridge: Unused cartridge: Store unopened containers refrigerated between 2°C and 8°C. Do not freeze. Do not expose to excessive heat or direct sunlight.
After cartridge insertion: Do not refrigerate in-use cartridges in reusable injectors. Store in-use drug product (after the disc seal has been punctured) unrefrigerated for up to 28 days at a maximum temperature of 30°C. The pen with the inserted cartridge should not be stored with the needle attached.
Shelf-life: Unused cartridge: 24 months.
After cartridge insertion: 28 days.
Vial: Do not freeze. Do not expose to excessive heat or direct sunlight.
Unopened vial: Store in a refrigerator (2°C - 8°C).
After first use: Store below 30°C for up to 28 days.
Shelf life: Unopened vial: 3 years.
After first use: 28 days.
KwikPen: Unused prefilled pens: Store in a refrigerator (2°C‑8°C) until time of use.
After first use: Store in‑use drug product (after disc seal has been punctured) unrefrigerated for up to 28 days at a maximum temperature of 30°C.
Do not freeze. Do not expose to excessive heat or direct sunlight.
Shelf‑life: Unused pre‑filled pens: 2 years.
After first use: 28 days.

Action

Pharmacotherapeutic group: Cartridge and Vial: Insulins and analogues for injection, intermediate-acting. KwikPen: Insulins and analogues for injection, intermediate acting combined with fast acting. ATC code: Vial: A10A C01. KwikPen: A10A D01.
Pharmacology: Pharmacodynamics: Insulin Human (rDNA) (Humulin N) is an intermediate acting insulin preparation.
The prime activity of insulin is the regulation of glucose metabolism.
In addition, insulin has several anabolic and anti-catabolic actions on a variety of different tissues. Within muscle tissue this includes increasing glycogen, fatty acid, glycerol and protein synthesis and amino acid uptake, while decreasing glycogenolysis, gluconeogenesis, ketogenesis, lipolysis, protein catabolism and amino acid output.
The typical activity profile (glucose utilization curve) following subcutaneous injection is illustrated as follows by the heavy line. Variations that a patient may experience in timing and/or intensity of insulin activity are illustrated by the shaded area. Individual variability will depend on factors such as size of dose, site of injection temperature and physical activity of the patient.
Cartridge: See Figure 1.


Vial: See Figure 2.


KwikPen: See Figure 3.


Pharmacokinetics: The pharmacokinetics of insulin do not reflect the metabolic action of that hormone. Therefore, it is more appropriate to examine glucose utilization curves when considering the activity of insulin.
Toxicology: Preclinical safety data: Humulin is human insulin produced by recombinant technology. No serious events have been reported in subchronic toxicology studies. Human insulin was not mutagenic in a series of in vitro and in vivo genetic toxicity assays.

MedsGo Class

Insulin Preparations