Humulin 70/30

Biphasic isophane insulin human (70% isophane insulin/30% soluble insulin, recombinant DNA origin).

Cartridge: Each mL contains 100 IU Human Insulin (produced in E. coli by recombinant DNA technology), Ph. Eur. (70% Isophane Insulin / 30% Soluble Insulin), 1.6 mg metacresol distilled and 0.65 mg phenol as preservatives.
Biphasic Isophane Insulin (70% Isophane Insulin / 30% Soluble Insulin) is a sterile suspension of human insulin in the proportion of 70% isophane insulin to 30% soluble insulin.
Vial: Each vial of Insulin Human (70% Isophane Insulin/30% Soluble Insulin) (rDNA origin) [Humulin 70/30] contains 100 IU/mL.
Insulin Human (70% Isophane Insulin/30% Soluble Insulin) (rDNA origin) [Humulin 70/30] is a sterile suspension. It is a mixture of isophane suspension and human insulin injection in proportion of 70/30%. It is an intermediate-acting insulin combined with the more rapid onset of action of regular insulin. The duration of activity may last up to 24 hours following injection.
KwikPen: 1 mL contains 100 IU human insulin (produced in E. coli by recombinant DNA technology).
One prefilled pen contains 3 mL equivalent to 300 IU of biphasic isophane insulin - 30% soluble insulin/70% isophane insulin.
Humulin 70/30 is a sterile suspension of human insulin in the proportion of 30% soluble insulin to 70% isophane insulin.
Excipients/Inactive Ingredients: Cartridge and KwikPen: 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: Cartridge: Biphasic Isophane Insulin (70% Isophane Insulin / 30% Soluble Insulin) (Humulin 70/30). ATC code: A10A D01.
Pharmacology: Vial: Insulin Human (Humulin) is synthesized in a special non-disease-producing laboratory strain of Escherichia coli bacteria that has been genetically altered by the addition of the gene for human insulin production. The time course of action of any insulin may vary considerably in different individuals or at different times in the same individual. As with all insulin preparations, the duration of action of Insulin Human (Humulin), is dependent on dose, site of injection, blood supply, temperature, and physical activity.
Pharmacodynamics: Cartridge and KwikPen: 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 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: Biphasic Isophane Insulin (70% Isophane Insulin / 30% Soluble Insulin) (Humulin 70/30) is an intermediate acting insulin preparation.
Biphasic Isophane Insulin (70% Isophane Insulin / 30% Soluble Insulin) (Humulin 70/30): see Figure 1.

Click on icon to see table/diagram/image

KwikPen: Humulin 70/30 is an intermediate-acting insulin preparation. (See Figure 2.)

Click on icon to see table/diagram/image

Pharmacokinetics: Cartridge and KwikPen: 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 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.

Cartridge and KwikPen: 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.
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.
Cartridge: 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.
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: Dosage schedule has been individualized for each patient, because each case of diabetes is different. Consult a physician on the type of insulin, dosage strength and when to inject the insulin.
The usual insulin dose may be affected by changes in food intake, activity or work schedule. The patient should carefully follow the physician's instructions to allow for these changes. Other things that may affect the insulin dose are: Illness: Illness, especially with nausea and vomiting, may cause insulin requirements to change. Even if the patient is not eating, insulin will still be required. The patient and the physician should establish a sick-day plan to use in case of illness. When sick, test blood/urine frequently and the patient should consult physician as instructed.
Pregnancy: Good control of diabetes is especially important for the patient and the unborn baby. Pregnancy may make managing diabetes more difficult. If planning to be pregnant, already pregnant, or nursing a baby, consult a doctor.
Medication: Insulin requirements may be increased if the patient is taking other drugs with hyperglycemic activity, such as oral contraceptives, corticosteroids, or thyroid replacement therapy. Insulin requirements may be reduced in the presence of drugs with hypoglycemic activity, such as oral hypoglycemics, salicylates (for example, aspirin), sulfa antibiotics, and certain antidepressants. Always discuss any medications that are being taken to the doctor (see also PRECAUTIONS).
Exercise: Exercise may lower the body's need for insulin during and for some time after the activity. Exercise may also speed up the effect of an insulin dose, especially if the exercise involves the area of injection site (eg, the leg should not be used for injection just prior to running). Discuss with the physician how to adjust dosage regimen to accommodate exercise.
Travel: Persons traveling across more than 2 time zones should consult their doctor concerning adjustments in their insulin schedule.
Kwikpen: 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.
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.
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. 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 Insulin Human (Humulin) or to the formulation excipients, unless used as part of a desensitization program.
Under no circumstances should any Insulin Human (Humulin) formulation other than Soluble Insulin Human (Humulin R) be given intravenously.

Cartridge and KwikPen: 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 may be 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.
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.
Vial and KwikPen: Thiazolidinediones (TZDs) used in combination with Insulin: TZDs in combination with insulin, are associated with an increase risk of edema and heart failure; especially in patients with underlying cardiac disease.
Cartridge: 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.
Vial: Hyperglycemia and Diabetic Acidosis: Hyperglycemia (too much glucose in the blood) may develop if the body has too little insulin.
Hyperglycemia can be brought about by: Omitting insulin intake or taking less than the physician has prescribed; eating significantly more than the suggested meal plan and developing fever, infection or other significant stressful situation.
In patients with insulin-dependent diabetes, prolonged hyperglycemia can result in diabetic acidosis. The first symptoms of diabetic acidosis usually come on gradually over a period of hours or days, and include a drowsy feeling, flushed face, thirst, loss of appetite and fruity odor of the breath. With acidosis, urine tests show large amounts of glucose and acetone. Heavy breathing and rapid pulse are more severe symptoms. If uncorrected, prolonged hyperglycemia or diabetic acidosis can lead to nausea, vomiting, dehydration, loss of consciousness or death. Therefore, it is important that the patient obtain medical assistance immediately.
Lipodystrophy: Rarely, administration of insulin subcutaneously can result in lipoatrophy (depression in the skin) or lipohypertrophy (enlargement or thickening of tissue). If either of these conditions is noticed, consult a physician. A change in the injection technique may help alleviate the problem.
Allergy to Insulin: Local Allergy: Patients occasionally experience redness, swelling and itching at the site of injection of insulin. This condition, called local allergy, usually clears up in a few days to a few weeks. In some instances, this condition may be related to factors other than insulin eg, irritants in the skin cleansing agent or poor injection technique. If local reactions occur, consult a physician.
Systemic Allergy: Less common, but potentially more serious, is generalized allergy to insulin, which 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. If generalized allergic reaction to insulin occur, notify a physician immediately.
Spontaneous Data: Cases of edema have been reported with insulin therapy, particularly if previous poor metabolic control is improved by intensified therapy.
Use in Pregnancy: Good control of diabetes is especially important for the patient and the unborn baby. Pregnancy may make managing diabetes more difficult. If planning to be pregnant, already pregnant, or nursing a baby, consult a physician.

Cartridge and KwikPen: 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.
Vial: Good control of diabetes is especially important for the patient and the unborn baby. Pregnancy may make managing diabetes more difficult. If planning to be pregnant, already pregnant, or nursing a baby, consult a physician.

Cartridge and KwikPen: 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), 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). 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 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 national reporting system.
Vial: Hypoglycemia (Insulin Reaction): Hypoglycemia (too little glucose in the blood) is one of the most frequent adverse events experienced by insulin users. It can be brought about by: Taking too much insulin; missing or delaying meals; exercising or working more than usual; an infection or illness (especially with diarrhea or vomiting); a change in the body's need for insulin; diseases of the adrenal, pituitary or thyroid gland, or progression of kidney or liver disease; interactions with other drugs that lower blood glucose eg, oral hypoglycemics, salicylates (eg, aspirin), sulfa antibiotics and certain antidepressants; consumption of alcoholic beverages.
Symptoms of mild to moderate hypoglycemia may occur suddenly and can include: sweating, dizziness, palpitation, tremor, hunger, restlessness, tingling in the hands, feet, lips or tongue, lightheadedness, inability to concentrate, headache, drowsiness, sleep disturbances, anxiety, blurred vision, slurred speech, depressive mood, irritability, lightheadedness, inability to concentrate, headache, abnormal behavior, unsteady movement and personality changes.
Signs of severe hypoglycemia can include: Disorientation, unconsciousness, seizures and death.
Therefore, it is important that assistance be obtained immediately.
Early warning symptoms of hypoglycemia may be different or less pronounced under certain conditions eg, long duration of diabetes, diabetic nerve disease, medications eg, beta-blockers, change in insulin preparations, intensified control (3 or more insulin injections per day) of diabetes.
A few patients who have experienced hypoglycemic reactions after transfer from animal-source insulin to human insulin have reported that the early warning symptoms of hypoglycemia were less pronounced or different from those experienced with their previous insulin.
Without recognition of early warning symptoms, the patient may not be able to take steps to avoid more serious hypoglycemia. Be alert for all the various types of symptoms that may indicate hypoglycemia. Patients who experience hypoglycemia without early warning symptoms should monitor their blood glucose frequently, especially prior to activities eg, driving. If the blood glucose is below the normal fasting glucose, consider eating or drinking sugar-containing foods to treat hypoglycemia.
Mild to moderate hypoglycemia may be treated by eating foods or drinks that contain sugar. Patients should always carry a quick source of sugar eg, candy mints or glucose tablets. More severe hypoglycemia may require the assistance of another person. Patients who are unable to take sugar orally or who are unconscious require an injection of glucagon or should be treated with IV administration of glucose at a medical facility.
The patient should learn to recognize the symptoms of hypoglycemia. If uncertain about these symptoms, the patient should monitor his/her blood glucose frequently to help him/her learn to recognize the symptoms that the patient experiences with hypoglycemia.
If the patient has frequent episodes of hypoglycemia or experience difficulty in recognizing the symptoms, he/she should consult the physician to discuss possible changes in therapy, meal plans and/or exercise programs to help avoid hypoglycemia.

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.

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) 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.
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 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 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.
KwikPen: For prefilled insulin delivery devices containing human insulin mixture (Humulin 70/30), roll the device between the palms10 times. Holding the device by one end, invert it 180° slowly 10 times to allow the glass bead to travel the full length of the cartridge with each inversion.
Insulin should look uniformly cloudy or milky after mixing. If not, repeat the above steps until the contents are mixed. Prefilled insulin delivery devices should be examined frequently. Do not use if the insulin substance (the white material) remains visibly separated from the liquid after mixing. Do not use if there are clumps in the insulin after mixing. Do not use if solid white particles stick to the bottom or wall of the cartridge, giving a frosted appearance.
Prepare your syringe prior to injection, as directed by your doctor or diabetes specialist nurse.
Use an insulin syringe marked for the strength of insulin being administered. Follow the instructions with Humulin 70/30 KwikPen for attaching the needle and administering the insulin injection.
For 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 may result in an inaccurate dose. For complete instructions on how to administer insulin, refer to the manufacturer's instruction for the insulin delivery device.
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.

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 and KwikPen: Store in a refrigerator (2°C-8°C). Do not freeze. Do not expose to excessive heat or direct sunlight.
When in use the Insulin Human (Humulin) vials/Humulin 70/30 KwikPen should not be refrigerated, but should be kept as cool as possible (below 30°C). Once in use the Insulin Human (Humulin) vials/Humulin 70/30 KwikPen may be used for up to 28 days. Do not use beyond this period.
KwikPen: Keep the container in the outer carton.

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.

Rx

Inj (cartridge) 100 u/mL x 3 mL x 5's, (vial) 100 IU/mL x 10 mL x 1's. Kwikpen susp for inj (pre-filled pen) 100 IU/mL x 3 mL x 5's.