Humulin N

Cartridge: Each mL contains 100 IU Human Insulin (produced in E. coli by recombinant DNA technology), Ph Eur., 1.6 mg metacresol distilled and 0.65 mg phenol as preservatives.
Vial: 1 mL contains 100 IU insulin human, Ph. Eur. (produced in E. coli by recombinant DNA technology).
One vial contains 10 mL equivalent to 1000 IU of isophane insulin.
KwikPen: 1 mL contains 100 IU human insulin, Ph. Eur. (produced in E. coli by recombinant DNA technology).
One prefilled pen contains 3 mL equivalent to 300 IU of isophane insulin.
Excipients/Inactive Ingredients: Cartridge: m-cresol, glycerol, phenol, protamine sulfate, dibasic sodium phosphate 7H₂O, zinc oxide, water for injections.
The following may be used to adjust pH: hydrochloric acid and/or sodium hydroxide.
Vial: m-cresol, Glycerol, Phenol, Protamine sulfate, Dibasic sodium phosphate 7H₂O, Zinc oxide, Water for injection.
The following may be used to adjust pH; hydrochloric acid and/or sodium hydroxide.
KwikPen: Metacresol distilled (1.6 mg/mL) as preservative, Glycerol, Phenol (0.65 mg/mL) as preservative, Protamine sulfate, Dibasic sodium phosphate, Zinc oxide, Water for injection.
The following may be used to adjust pH: hydrochloric acid and/or sodium hydroxide.

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.

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Vial: See Figure 2.

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KwikPen: See Figure 3.

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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: Insulin Human (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.

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

Posology: The dosage should be determined by the physician, according to the requirement of the patient.
Insulin Human (rDNA) (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 Insulin Human preparation 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.
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).
Vial: Pediatric population: No data are available.
Method of Administration: Vial: 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 in order to reduce the risk of lipodystrophy and cutaneous amyloidosis (see Precautions and Adverse Reactions).

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.

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.
Vial: Hypersensitivity to the active substance or to any of the excipients listed in Description, unless used as part of a desensitization program.
Under no circumstances should any Insulin Human (rDNA) (Humulin N) 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), 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, or 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.
Vial: Patients must be instructed to perform continuous rotation of the injection site to reduce the risk of developing lipodystrophy and cutaneous amyloidosis. There is a potential risk of delayed insulin absorption and worsened glycaemic control following insulin injections at sites with these reactions. A sudden change in the injection site to an unaffected area has been reported to result in hypoglycaemia. Blood glucose monitoring is recommended after the change in the injection site, and dose adjustment of antidiabetic medications may be considered.
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.
Traceability: Vial: In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded.
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.

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.

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 Isophane 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).
Vial: Skin and subcutaneous tissue disorders: Frequency "unknown": Cutaneous amyloidosis.
Skin and subcutaneous tissue disorders: Lipodystrophy and cutaneous amyloidosis may occur at the injection site and delay local insulin absorption. Continuous rotation of the injection site within the given injection area may help to reduce or prevent these reactions (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.

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.

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.

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.

KwikPen: PLEASE READ THESE INSTRUCTIONS BEFORE USE: Read the Instructions for Use before you start taking your insulin and each time you get another KwikPen. There may be new information. This information does not take the place of talking to your healthcare provider about your medical condition or your treatment.
KwikPen ("Pen") is a disposable prefilled pen containing 300 units of insulin. You can give yourself multiple doses using one Pen. The Pen dials 1 unit at a time. You can give from 1 to 60 units in a single injection. If your dose is more than 60 units, you will need to give yourself more than one injection. The plunger only moves a little with each injection, and you may not notice that it moves. The plunger will only reach the end of the cartridge when you have used all 300 units in the Pen.
Do not share your Pen with other people, even if the needle has been changed. Do not reuse or share needles with other people. You may give an infection to them or get an infection from them.
This Pen is not recommended for use by the blind or visually impaired persons without the help of someone trained to use the Pen.
How to recognize your Insulin Human (Humulin N KwikPen): Pen Body Color: Beige.
Labels: White with Light Green Color Bar.
Supplies needed to give your injection: Insulin Human (Humulin N KwikPen), KwikPen compatible Needle [BD Pen Needles recommended], Alcohol swab.
Preparing your KwikPen: Wash your hands with soap and water.
Check the Pen to make sure you are taking the right type of insulin. This is especially important if you use more than 1 type of insulin.
Do not use your Pen past the expiration date printed on the label. After you start using the Pen, throw your Pen after the in-use time of 28 days.
Always use a new Needle for each injection to help prevent infections and blocked Needles.
Step 1: Pull the Pen Cap off.
Do not remove the Pen Label.
Wipe the Rubber Seal with an alcohol swab.
Step 2: Gently roll the Pen 10 times and invert the Pen 10 times.
Mixing is important to make sure you get the right dose. The insulin should look evenly mixed.
Step 3: Check the appearance of the insulin.
Insulin Human (Humulin N KwikPen) should look white and cloudy after mixing. Do not use if it looks clear or contains any lumps or particles.
Step 4: Select a new Needle.
Pull off the Paper Tab from the Outer Needle Shield.
Step 5: Push the capped Needle straight onto the Pen and twist the Needle on until it is tight.
Step 6: Pull off the Outer Needle Shield. Do not throw it away.
Pull off the Inner Needle Shield and throw it away.
Priming KwikPen: Prime before each injection.
Priming your Pen means removing the air from the Needle and Cartridge that may collect during normal use and ensures that the Pen is working correctly.
If you do not prime before each injection, you may get too much or too little insulin.
Step 7: To prime your Pen, turn the Dose Knob to select 2 units.
Step 8: Hold your Pen with the Needle pointing up. Tap the Cartridge Holder gently to collect air bubbles at the top.
Step 9: Continue holding your Pen with Needle pointing up. Push the Dose Knob in until it stops, and "0" is seen in the Dose Window. Hold the Dose Knob in and count to 5 slowly.
You should see insulin at the tip of the Needle.
If you do not see insulin, repeat the priming steps, but not more than 4 times.
If you still do not see insulin, change the Needle and repeat the priming steps.
Small air bubbles are normal and will not affect your dose.
Selecting Your Dose: You can give from 1 to 60 units in a single injection.
If your dose is more than 60 units, you will need to give more than one injection.
If you need help deciding how to divide up your dose, ask your healthcare provider.
You should use a new Needle for each injection and repeat the priming step.
Step 10: Turn the Dose Knob to select the number of units you need to inject. The Dose Indicator should line up with your dose.
The Pen dials 1 unit at a time.
The Dose Knob clicks as you turn it.
DO NOT dial your dose by counting the clicks because you may dial the wrong dose.
The dose can be corrected by turning the Dose Knob in either direction until the correct dose lines up with the Dose Indicator.
The even numbers are printed on the dial.
The odd numbers, after the number 1, are shown as full lines.
Always check the number in the Dose Window to make sure you have dialed the correct dose.
The Pen will not let you dial more than the number of units left in the Pen.
If you need to inject more than the number of units left in the Pen, you may either: inject the amount left in your Pen and then use a new Pen to give the rest of your dose, or get a new Pen and inject the full dose.
It is normal to see a small amount of insulin left in the Pen that you cannot inject.
Giving your injection: Inject your insulin as your healthcare provider has shown you.
Change (rotate) your injection site for each injection.
Do not try to change your dose while injecting.
Step 11: Choose your injection site.
Your insulin is injected under the skin (subcutaneously) of your stomach area, buttocks, upper legs or upper arms.
Wipe the skin with an alcohol swab, and let the injection site dry before you inject your dose.
Step 12: Insert the Needle into your skin.
Push the Dose Knob all the way in.
Continue to hold the Dose Knob in and slowly count to 5 before removing the Needle.
Do not try to inject your insulin by turning the Dose Knob. You will NOT receive your insulin by turning the Dose Knob.
Step 13: Pull the Needle out of your skin.
A drop of insulin at the Needle tip is normal. It will not affect your dose.
Check the number in the Dose Window: If you see "0" in the Dose window, you have received the full amount you dialed.
If you do not see "0" in the Dose window, do not redial. Insert the needle into your skin and finish your injection.
If you still do not think you received the full amount you dialed for your injection, do not start over or repeat that injection. Monitor your blood glucose as instructed by your healthcare provider.
If you normally need to give 2 injections for your full dose, be sure to give your second injection.
The plunger only moves a little with each injection, and you may not notice that it moves.
If you see blood after you take the Needle out of your skin, press the injection site lightly with a piece of gauze or an alcohol swab. Do not rub the area.
After injection: Step 14: Carefully replace the Outer Needle Shield.
Step 15: Unscrew the capped Needle and dispose of it as described (see Disposing of Pens and Needles as follows).
Do not store the Pen with the Needle attached to prevent leaking, blocking the Needle, and air from entering the Pen.
Step 16: Replace the Pen Cap by lining up the Cap Clip with the Dose Indicator and pushing straight on.
Disposing of Pens and Needles: Put used Needles in a sharps container or a hard plastic container with a secure lid. Do not throw needles directly into your household trash.
The used Pen may be discarded in your household trash after you have removed the Needle.
Do not recycle the filled sharps container.
Ask your healthcare provider about options to dispose of the sharps container properly.
The directions regarding needle handling are not intended to replace local, healthcare provider or institutional policies.
Storing your Pen: Unused Pens: Store unused Pens in the refrigerator at 2°C to 8°C.
Do not freeze your insulin. Do not use if it has been frozen.
Unused Pens may be used until the expiration date printed on the label if the Pen has been kept in the refrigerator.
In-use Pen: Store the Pen you are currently using at room temperature not more than 30°C and away from heat and light.
Throw away the Pen you are using after 28 days from date of first use even if it still has insulin left in it.
General information about the safe and effective use of your Pen: Do not use your Pen if any part looks broken or damaged.
Always carry an extra Pen in case yours is lost or damaged.
Troubleshooting: If you cannot remove the Pen Cap, gently twist the cap back and forth, and then pull the cap straight off.
If the Dose Knob is hard to push: Pushing the Dose Knob more slowly will make it easier to inject.
Your Needle may be blocked. Put on a new Needle and prime the Pen.
You may have dust, food, or liquid inside the Pen. Throw the Pen away and get a new Pen.

Insulin Preparations

A10AC01 - insulin (human) ; Belongs to the class of intermediate-acting insulins and analogues. Used in the treatment of diabetes.

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