Humulin 70/30

Human insulin isophane, human insulin (recombinant DNA origin).

Humulin 70/30 is a premixed suspension which contains 30% insulin dissolved in water and 70% insulin with protamine sulphate.
Humulin 70/30 is a sterile suspension of human insulin in the proportion of 30% soluble insulin to 70% isophane insulin.
Cartridge: One cartridge contains 3 ml equivalent to 300 IU of biphasic isophane insulin - 30% soluble insulin/70% isophane insulin.
Vial: 1 ml contains 100 IU insulin human (produced in E. coli by recombinant DNA technology).
One vial contains 10 ml equivalent to 1000 IU of biphasic isophane insulin - 30% soluble insulin/70% isophane insulin.
Excipients/Inactive Ingredients: 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.

Pharmacotherapeutic group: Insulins and analogues for injection, intermediate acting combined with fast acting. ATC code: A10A D01.
Humulin 70/30 is a premixed suspension of rapid and intermediate acting insulin.
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 utilisation curve) following subcutaneous injection is illustrated below 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. (See figure.)

Click on icon to see table/diagram/image

Pharmacokinetics: The pharmacokinetics of insulin do not reflect the metabolic action of that hormone. Therefore, it is more appropriate to examine glucose utilisation curves (as discussed previously) 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.

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.
Paediatric population: No data are available.
Method of administration: Humulin 70/30 should be given by subcutaneous injection but may, although not recommended, also be given by intramuscular 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 in order to reduce the risk of lipodystrophy and cutaneous amyloidosis (see Precautions and Adverse Reactions).
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 mixture 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.

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.

Hypoglycaemia.
Hypersensitivity to the active substance or to any of the excipients listed in Description, unless used as part of a desensitisation programme.
Under no circumstances should any Humulin formulation other than Humulin R 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 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.
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 oedema. Pioglitazone should be discontinued, if any deterioration in cardiac symptoms occurs.
Traceability: 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: 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 hypoglycaemia. 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 hypoglycaemia whilst driving, this is particularly important in those who have reduced or absent awareness of the warning signs of hypoglycaemia or have frequent episodes of hypoglycaemia. 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.

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).
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).
Cases of oedema have been reported with insulin therapy, particularly if previous poor metabolic control is improved by intensified insulin therapy.
Reporting of suspected adverse reactions: Reporting suspected adverse reactions after authorisation 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 via the Drug Office, Department of Health.

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 hyperglycaemic activity, such as glucocorticoids, thyroid hormones, growth hormone, danazol, beta₂-sympathomimetic (such as ritodrine, salbutamol, terbutaline), 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.

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 and vials can be used until empty, then properly discard. Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
Instructions for use and handling: Cartridge: A suspension for injection in a 3 ml cartridge to be used with a CE marked pen as recommended in the information provided by the device manufacturer.
Preparing a Dose: Cartridges containing 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 above 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.
The manufacturer's instructions with each individual pen must be followed for loading the cartridge, attaching the needle and administering the insulin injection.
Injecting a Dose: Inject the correct dose of insulin.
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 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 uniformly cloudy or milky. If not, repeat the above 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.
Incompatibilities: Humulin preparations should not be mixed with insulins produced by other manufacturers or with animal insulin preparations.

Cartridge: Unused Cartridges: Store in a refrigerator (2°C-8°C). Do not freeze. Do not expose to excessive heat or direct sunlight.
After Cartridges Insertion: Store below 30°C. Do not refrigerate. The pen with the inserted cartridge should not be stored with the needle attached.
Shelf life: After Cartridges Insertion: 28 days.
Vial: Do not freeze.
Store unopened containers refrigerated at 2°C to 8°C until time of use.
The drug product should be stored and used protected from freezing, from direct heat, and from direct light or sunlight.
Shelf life: Unopened vials: Shelf life is 36 months when stored at 2°C to 8°C and when protected from light.
After first use: Store drug product in a refrigerator at 2°C to 8°C until time of use.
Store in-use drug product (after the stopper has been punctured) refrigerated or unrefrigerated for up to 28 days at a maximum temperature of 30°C.

Insulin Preparations

A10AD01 - insulin (human) ; Belongs to the class of intermediate-acting combined with fast-acting insulins and analogues. Used in the treatment of diabetes.

P₁