Indications/Uses
For the treatment of patients with diabetes mellitus who require insulin for the maintenance of glucose homeostasis.
Dosage/Direction for Use
Cartridge: The dosage should be determined by the physician, according to the requirement of the patient.
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.
Biphasic Isophane Insulin (70% Isophane Insulin/30% Soluble Insulin) (Humulin 70/30) should be given by subcutaneous injection. This formulation should not be administered intravenously.
Care should be taken when injecting any Insulin Human (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.
Biphasic Isophane Insulin (70% Isophane Insulin/30% Soluble Insulin) (Humulin 70/30) formulation is a ready-made defined mixture of soluble and 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.
Vial and KwikPen: Posology: The dosage should be determined by the physician, according to the requirement of the patient.
Pediatric population: No data are available.
Method of administration: Insulin Human (Humulin 70/30) 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.
Insulin Human [Humulin 70/30] formulation is a ready-made defined mixture of isophane and soluble 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.
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, 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.
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 Humulin 70/30, 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).
Spontaneous data: 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 medicinal products 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.
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.
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.
KwikPen: Insulin requirements may be increased by substances with hyperglycaemic activity, such as oral contraceptives, glucocorticoids, thyroid hormones, growth hormone, danazol, beta2-sympathomimetics (such as ritodrine, salbutamol, terbutaline), thiazides.
Caution For Usage
Incompatibilities: Humulin 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: Cartridge: a) Preparing a dose: Cartridges of Biphasic Isophane Insulin (70% Isophane Insulin/30% Soluble Insulin) (Humulin 70/30) 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. 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.
The manufacturer's instructions with each individual pen must be followed for loading the cartridge, attaching the needle and administering the insulin injection.
b) Injecting a dose: Inject the correct dose of insulin, as directed by your 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.
Vial: A suspension for injection in a 10 mL vial to be used in conjunction with an appropriate syringe (100 IU/mL markings).
a) Preparing a dose: Vials containing Insulin Human [Humulin 70/30] formulation should be rotated several times in the palms of the hands before use to completely resuspend the insulin, until it appears uniform 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.
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: To prevent the possible transmission of disease, each pen must be used by one patient only, even if the needle is changed.
A suspension for injection in a prefilled pen injector containing 3 mL cartridge. Insulin Human (Humulin 70/30 KwikPen) delivers up to 60 units per dose in single increments.
a) Preparing a dose: Insulin Human (Humulin 70/30 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 70/30 KwikPen) for attaching the needle and administering the insulin injection.
Insulin Human (Humulin 70/30 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 70/30 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.
Each pack contains a patient information leaflet with instruction on how to inject insulin.
Storage
Cartridge: Unused cartridge: Store unopened containers refrigerated between 2°C - 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 cartridges (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 vials: Store in a refrigerator (2°C - 8°C).
After first use: Store below 30°C for up to 28 days.
Shelf life: Unopened vials: 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 prefilled pens: 2 years.
After first use: 28 days.
Action
Pharmacotherapeutic group: Insulins and analogues for injection, intermediate acting combined with fast acting. ATC code: A10A D01.
Cartridge: Biphasic Isophane Insulin (70% Isophane Insulin/30% Soluble Insulin) (Humulin 70/30) is an intermediate acting insulin preparation.
Vial: Biphasic Isophane Insulin Human (70% Isophane Insulin + 30% Soluble Insulin) [Humulin 70/30] is a premixed suspension of intermediate and rapid acting insulin.
KwikPen: Insulin Human (Humulin 70/30 KwikPen) is an intermediate-acting insulin preparation.
Pharmacology: Pharmacodynamics: 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 (as discussed previously) when considering the activity of insulin.
Toxicology: Preclinical safety data: Humulin 70/30 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
Features
- Insulin Human