This combination insulin injection is indicated for:

• Treatment of all patients with Type 1 diabetes
• Treatment of Type 2 diabetes mellitus not adequately controlled by diet and/or oral hypoglycemic agents
• Initial stabilization of diabetes in conditions such as diabetic ketoacidosis, hyperosmolar non-ketotic syndrome, and during stress conditions like severe infections or major surgery
• Management of gestational diabetes

30/70: Each mL suspension contains Insulin Human (rDNA) USP 100 IU (equivalent to 3.47 mg) as 30% Regular Insulin Human and 70% Isophane Insulin Human.

50/50: Each mL suspension contains Insulin Human (rDNA) USP 100 IU (equivalent to 3.47 mg) as 50% Regular Insulin Human and 50% Isophane Insulin Human.

Insulin lowers blood glucose by facilitating cellular uptake of glucose after binding to insulin receptors on muscle and fat cells, and by inhibiting hepatic glucose production.Insulin has a very short plasma half-life of a few minutes and does not show significant binding to plasma proteins.

After subcutaneous administration, the action profile is:

• Onset of action: within 30 minutes
• Peak effect: 1–3 hours
• Duration of action: approximately 18–24 hours

Dosage is individual and determined by the physician in accordance with the needs of the patient.

The average range of total daily insulin requirement for maintenance therapy in type 1 diabetic patients lies between 0.5 and 1.0 IU/Kg. In pre-pubertal children it usually varies from 0.7 to 1.0 IU/ Kg.

The daily insulin requirement may be higher in patients with insulin resistance (e.g. during puberty in the young or due to obesity) and lower in patients with endogenous insulin production or during the period of partial remission.

Initial dosage for type 2 diabetic patients are often lower, e.g. 0.3 to 0.6 IU/ Kg/ Day.

An injection should be followed within 30 minutes by a meal or snack containing carbohydrates.

Administration

• It is usually administered subcutaneously in the abdominal wall. The thigh, the gluteal region or the deltoid region may also be used.
• Subcutaneous injection into the abdominal wall ensures a faster absorption than from other injection sites.
• In order to avoid lipodystrophy, injection sites for a given insulin preparation should be rotated within an anatomic region.

Dosage Adjustment

• Concomitant illness, especially infections and feverish conditions, usually increases the patient's insulin requirement.
• Renal or hepatic impairment may reduce insulin requirement.
• Adjustment of the dosage may also be necessary if patients change physical activity or their usual diet.
• Dosage adjustment may be necessary when transferring patients from one insulin preparation to another.

Before using insulin 30/70

• Make sure it is the right type of insulin
• Always check the cartridge including the rubber plunger (stopper)
• Disinfect the rubber membrane with surgical spirit

Do not use insulin 30/70

• If cartridge or the device containing cartridge is dropped or crushed, there is a risk of damage and leakage of insulin
• If it has not been stored correctly or been frozen
• If it is not uniformly white and cloudy when it is mixed

Mixing the insulin

• Before putting the cartridge into the insulin delivery system, move it slowly up and down between positions A and B and back (see the picture) so that the glass ball moves from one end of the cartridge to the other. Repeat this movement before first use at least 20 times and for every injection at least 10 times. The movement should always be repeated until the liquid appears uniformly white and cloudy. Complete the other stages of injection without delay.
• If the cartridge is already inside the insulin delivery system, move the delivery system slowly up and down between A and B and back with the cartridge inside at least 10 times. Do this again before every injection.

How to inject this insulin

• Inject the insulin under the skin. Use the injection technique described in the delivery system manual.
• Keep the needle under the skin for at least 6 seconds to make sure that the full dose has been delivered.
• After each injection be sure to remove the needle. Otherwise the liquid may leak out when the temperature changes and the strength of the insulin may change.

Concomitant use of other drugs may alter insulin requirements.

Drugs that may reduce insulin requirement: Oral hypoglycemic agents (OHA), monoamine oxidase inhibitors (MAOI), non-selective beta-blockers, ACE inhibitors, salicylates, and alcohol.

Drugs that may increase insulin requirement: Thiazide diuretics, glucocorticoids, thyroid hormones, beta-sympathomimetics, growth hormone, and danazol.

Beta-blockers may mask hypoglycemia symptoms and delay recovery. Octreotide/Lanreotide may increase or decrease insulin needs. Alcohol may intensify and prolong hypoglycemic effects.

Insulin should not be used in patients with hypoglycemia or known hypersensitivity to human insulin or any excipients.

The most common adverse effect is hypoglycemia, usually dose-related. Other possible effects include: Lipodystrophy at injection site, Allergic reactions (rash, itching, sweating, GI upset, angioedema, breathing difficulty, palpitations, hypotension), Generalized hypersensitivity reactions (may be life-threatening) Edema at treatment initiation (usually temporary).

Insulin is safe during pregnancy as it does not cross the placenta. Both hypo- and hyperglycemia increase fetal risk. Insulin requirements decrease in the first trimester and increase in the second and third trimesters. After delivery, requirements return quickly to pre-pregnancy levels. Insulin is safe during breastfeeding, but dose adjustment may be needed.

Inadequate dosing or abrupt discontinuation of insulin therapy, particularly in Type 1 diabetes, may result in hyperglycemia.

Persistent untreated hyperglycemia in Type 1 diabetes can progress to diabetic ketoacidosis, which is potentially fatal.

Hypoglycemia may occur if insulin dose exceeds the patient’s requirement.

Switching to a different insulin type or brand should only be done under strict medical supervision.

Any change in insulin strength, manufacturer, formulation (rapid-, intermediate-, or long-acting), source (human/animal/analogue), or production method may require dose adjustment.

Patients traveling across different time zones should consult a physician, as timing of insulin administration and meals may need modification.

Do not use insulin if clumping is observed after mixing or if white particles or a frosted appearance is seen in the vial.

There is no specific defined overdose limit for insulin. However, hypoglycemia may occur in stages:

Mild hypoglycemia: Managed with oral glucose or sugar-containing foods.

Severe hypoglycemia (loss of consciousness): Treated with Glucagon (0.5–1 mg) given intramuscularly or subcutaneously by trained personnel, or intravenous glucose by healthcare professionals.

If no response to glucagon within 10–15 minutes, intravenous glucose must be administered.

After recovery, oral carbohydrates should be given to prevent recurrence of hypoglycemia.

Store at 2°C–8°C in a refrigerator. Do not freeze. Protect from light and excessive heat. Do not refrigerate during use. In-use cartridge may be used up to: 6 weeks if stored below 25°C, 4 weeks if stored below 30°C. Mix gently (roll between hands) before use.