Insuvit® 30/70
UkraineTable of Contents
INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT INSUVIT® 30/70 (INSUVIT® 30/70)
Composition:
Active substance: insulin (human);
1 ml of suspension consisting of 30% human insulin solution and 70% isophane human insulin suspension contains 100 IU of human insulin (recombinant DNA);
Excipients: metacresol, zinc oxide, glycerol, phenol liquefied, protamine sulfate, anhydrous sodium hydrogen phosphate, hydrochloric acid diluted or sodium hydroxide solution, water for injections.
Pharmaceutical form. Injection suspension.
Main physicochemical properties: white-colored suspension, which during storage may separate into a colorless or almost colorless supernatant liquid and a white sediment that readily resuspends upon shaking.
Pharmacotherapeutic group. Antidiabetic agents. Insulins and analogues for injection, intermediate- and long-acting in combination with short-acting insulin (human).
ATC code A10AD01.
Pharmacological properties
Pharmacodynamics
The blood glucose-lowering effect of insulin is due to its promotion of glucose uptake by tissues following insulin binding to receptors on muscle and fat cells, as well as simultaneous inhibition of glucose release from the liver.
Insuvit® 30/70 is a biphasic insulin preparation.
The average profile of action after subcutaneous injection is as follows:
onset of action – within 0.5 hours;
maximum effect – occurs 2–8 hours after administration;
duration of action – up to 24 hours.
Pharmacokinetics
The elimination half-life (t1/2) of insulin from blood is several minutes; therefore, the insulin activity profile is determined exclusively by its absorption characteristics. This process depends on a number of factors (e.g., insulin dose, injection method and site, subcutaneous fat thickness, type of diabetes), resulting in considerable variability in insulin effect among patients.
Absorption. The absorption profile is determined by the fact that this insulin is a mixture of insulin components characterized by rapid and prolonged absorption. The peak plasma concentration of short-acting insulin occurs within 1.5–2.5 hours after subcutaneous injection.
Distribution. No significant binding of insulin to plasma proteins has been observed, except for circulating antibodies against insulin (if present).
Metabolism. Human insulin is cleaved by insulin proteases or insulin-degrading enzymes and possibly by proteindisulfide isomerase. Several cleavage (hydrolysis) sites within the human insulin molecule are believed to exist. None of the metabolites formed after hydrolysis possess biological activity.
Elimination. The terminal t1/2 of insulin is determined by the rate of its absorption from the subcutaneous tissue. Therefore, the terminal t1/2 reflects the absorption rate rather than elimination per se of insulin from plasma (the t1/2 of insulin in circulation is only several minutes). According to available study data, t1/2 ranges from 5 to 10 hours.
Non-clinical safety data
Non-clinical studies on pharmacological safety (repeated-dose toxicity, genotoxicity, carcinogenicity, reproductive and developmental toxicity) revealed no hazard to humans associated with the use of this medicinal product.
Clinical characteristics.
Indications.
Treatment of diabetes mellitus.
Contraindications.
Hypoglycemia.
Hypersensitivity to human insulin or to any excipient of the medicinal product.
Interaction with other medicinal products and other forms of interaction.
It is known that a number of medicinal products affect glucose metabolism.
Medicinal products that may decrease insulin requirements: oral hypoglycemic agents (OHA), monoamine oxidase inhibitors (MAOI), non-selective β-blockers, angiotensin-converting enzyme (ACE) inhibitors, salicylates, anabolic steroids, and sulfonamides.
Medicinal products that may increase insulin requirements: oral contraceptives, thiazides, glucocorticoids, thyroid hormones, sympathomimetics, growth hormone, and danazol.
β-blockers may mask the symptoms of hypoglycemia and delay recovery from hypoglycemia.
Octreotide/lanreotide may either decrease or increase insulin requirements. Alcohol may potentiate or weaken the hypoglycemic effect of insulin.
Special precautions for use.
Hyperglycemia
Inadequate dosing or discontinuation of treatment (especially in type 1 diabetes) may lead to hyperglycemia and diabetic ketoacidosis. Typically, the first symptoms of hyperglycemia develop gradually over several hours or days. These include thirst, frequent urination, nausea, vomiting, drowsiness, skin redness and dryness, dry mouth, loss of appetite, as well as acetone breath odor.
In type 1 diabetes, untreated hyperglycemia leads to diabetic ketoacidosis, which is potentially life-threatening.
Hypoglycemia
Hypoglycemia may occur when insulin is administered at a dose that is too high relative to insulin requirements. Do not administer the medication in case of hypoglycemia or suspected hypoglycemia.
Skipping meals or unexpected physical exertion may lead to hypoglycemia.
Patients who have significantly improved glycemic control due to intensive insulin therapy may experience changes in the usual warning signs of hypoglycemia; such patients should be warned in advance.
Usual warning symptoms may disappear in patients with long-standing diabetes.
Concomitant diseases, particularly infections and febrile conditions, generally increase insulin requirements.
Concomitant kidney, liver, or adrenal gland disorders, as well as pituitary or thyroid gland diseases, may require adjustment of insulin dosage.
When a patient is switched to another type of insulin, symptoms of hypoglycemia may change or become less pronounced compared to those experienced with the previous insulin.
Switching from other insulins
Changing a patient to another type or formulation of insulin must be done under strict medical supervision.
Changes in insulin concentration, type (manufacturer), kind, origin (human insulin or human insulin analog), and/or production method (recombinant DNA technology or animal-sourced insulin) may necessitate insulin dose adjustments.
Patients switching to Insuvit® 30/70 from another insulin type may require an increased number of daily injections or changes in dosage compared to their previous insulin regimen. Dose adjustments may be necessary both at the initiation of the new medication and during the first weeks or months of its use.
Injection site reactions
With any insulin therapy, injection site reactions may occur, including pain, redness, itching, urticaria, swelling, bruising, and inflammation. Regularly changing the injection site, even within the same general area, may reduce or prevent these reactions. Such reactions usually resolve within a few days or weeks. Rarely, injection site reactions may require discontinuation of Insuvit® 30/70 therapy.
Patients should be advised to consistently rotate injection sites to reduce the risk of lipodystrophy and cutaneous amyloidosis. There is a potential risk of delayed insulin absorption and deterioration of glycemic control following insulin injections into affected areas. Switching injection sites to unaffected skin areas may lead to hypoglycemia. Monitoring of blood glucose levels is recommended after changing the injection site, and doses of antidiabetic medications should be adjusted as necessary.
Patients should consult their physician before traveling across time zones, as this alters the insulin injection and meal schedule.
Insulin suspensions must not be used in insulin pumps for continuous subcutaneous insulin infusion.
Combination of Insuvit® 30/70 with pioglitazones
Cases of congestive heart failure have been reported when pioglitazones are used in combination with insulin, particularly in patients with risk factors. This should be considered when prescribing combination therapy with pioglitazones and insulin. Patients receiving these drugs in combination should be monitored by a physician for early signs of congestive heart failure, weight gain, and development of edema. If any worsening of cardiac function occurs, treatment with pioglitazones should be discontinued.
To prevent accidental medication errors, patients must be warned to always check the label on the medication before each injection to avoid confusion between Insuvit® 30/70 and other insulin products.
Special populations
Elderly patients (≥ 65 years)
Insuvit® 30/70 can be used in elderly patients.
Enhanced monitoring of blood glucose levels and individualized insulin dose adjustments are recommended in elderly patients.
Renal and hepatic impairment
Renal and hepatic impairment may reduce insulin requirements. Enhanced blood glucose monitoring and individualized insulin dose adjustments are recommended in patients with renal or hepatic impairment.
Content of excipients
Insuvit® 30/70 contains less than 1 mmol of sodium (23 mg) per dose, i.e., it is practically sodium-free.
Use during pregnancy or breastfeeding
Since insulin does not cross the placental barrier, there are no restrictions on insulin treatment of diabetes during pregnancy.
Throughout pregnancy and in cases of suspected pregnancy, intensified monitoring of blood glucose levels and close supervision of diabetic pregnant women are recommended, as inadequate diabetes control—both hypoglycemia and hyperglycemia—increases the risk of fetal malformations and fetal death.
Insulin requirements usually decrease during the first trimester of pregnancy and significantly increase during the second and third trimesters.
After delivery, insulin requirements usually return rapidly to pre-pregnancy levels.
There are no restrictions on the use of Insuvit® 30/70 during breastfeeding, as maternal treatment poses no risk to the infant. However, dose adjustments and dietary modifications for the mother may be necessary.
Fertility
Reproductive toxicity studies in animals using human insulin have not revealed any adverse effects on fertility.
Ability to influence reaction speed when driving or operating machinery
A patient's reaction and ability to concentrate may be impaired during hypoglycemia. This may pose a risk in situations where such abilities are critical (e.g., when driving a car or operating machinery).
Patients should be advised to take preventive measures against hypoglycemia before driving. This is particularly important for patients with diminished or absent hypoglycemia warning symptoms or those who experience frequent hypoglycemic episodes. In such circumstances, the advisability of driving should be carefully considered.
Method of Administration and Dosage
Insuvit® 30/70 is a biphasic human insulin. It contains both short-acting insulin and long-acting insulin. Biphasic insulin preparations are usually administered once or twice daily when a rapid initial effect followed by a prolonged action is required.
Insuvit® 30/70 is a ready-to-use mixture of soluble insulin and isophane insulin. The patient's treatment regimen should be prescribed according to individual metabolic needs.
Dosage
The potency of human insulin is expressed in International Units (IU).
The insulin dosage is individual and determined by the physician according to the patient's needs. The individual daily insulin requirement is usually between 0.3 and 1.0 IU/kg/day. Daily insulin requirements may increase in patients with insulin resistance (e.g., during puberty or in obesity) and decrease in patients with residual endogenous insulin production.
The injection should be administered 30 minutes before a main or supplementary meal containing carbohydrates.
Dosage Adjustment
Concomitant diseases, particularly infections and febrile conditions, generally increase the patient's insulin requirements. Concomitant kidney, liver, or adrenal gland disorders, as well as diseases of the pituitary gland, thyroid gland, or hypothalamus, may necessitate changes in insulin dosage.
Dosage adjustments may also be required when there are changes in the patient's physical activity level or usual diet. Dose titration may also be necessary when switching patients to different insulin preparations.
Administration
Insuvit® 30/70 is intended for subcutaneous injection only. Insulin suspension must never be administered intravenously.
Insuvit® 30/70 is usually injected subcutaneously into the thigh or the abdominal wall. It may also be administered into the buttocks or the deltoid region of the shoulder.
Subcutaneous injections into the abdominal wall result in faster insulin absorption compared to injections into other body sites.
The duration of action depends on the dose, injection site, temperature, and level of physical activity. Injecting into a lifted skin fold significantly reduces the risk of intramuscular injection.
After injection, the needle should remain under the skin for at least 6 seconds to ensure complete delivery of the dose.
To reduce the risk of lipodystrophy and cutaneous amyloidosis, the injection site should always be rotated, even within the same body area (see sections of the instruction "Special Precautions" and
«Side effects»).
When administering an insulin preparation, avoid inserting the needle into a blood vessel. After administration, do not rub the injection site. Patients should be thoroughly instructed in the proper injection technique. Aseptic techniques must be followed when administering injections. To avoid purulent-inflammatory complications, do not reuse disposable syringes.
Do not use Inzuvit® 30/70:
- in infusion pumps;
- in case of allergy (hypersensitivity) to human insulin or to any other ingredient of the preparation;
- if hypoglycemia (low blood sugar) is suspected;
- if the cartridge or the device containing the cartridge has been dropped, damaged, or crushed;
- if the preparation has been stored improperly or has been frozen;
- if the insulin suspension does not become uniformly white and cloudy after mixing.
Before using Inzuvit® 30/70:
- ensure that the type of insulin corresponds to the prescribed one;
- always inspect the cartridge, including the rubber plunger (stopper); do not use the cartridge if there are any external damages.
How to use this insulin preparation
Inzuvit® 30/70 is administered by subcutaneous injection. Never inject insulin directly into a vein or muscle. Always rotate injection sites, even within the same body area, to reduce the risk of developing lumps or pitting of the skin. The best sites for self-injection are the front of the abdomen, buttocks, front of the thighs, or upper arms.
Insulin acts faster when injected into the abdominal area.
Inzuvit® 30/70 (in vials) should be administered using special insulin syringes with appropriate calibration.
Patients are advised to dispose of the needle and syringe after each injection.
Before administration, ensure that the syringe calibration corresponds to the insulin concentration indicated on the vial label. Use syringes only with calibration matching the insulin concentration in this vial.
- Disinfect the rubber stopper with an alcohol-soaked cotton swab.
- Gently roll the vial between your palms to mix its contents until the suspension becomes uniformly white and cloudy. Do not shake the vial vigorously, as this may cause foaming, which can interfere with accurate dose measurement.
- Draw into the syringe an amount of air equal to the insulin dose to be administered.
- Inject the air from the syringe into the insulin vial.
- Gently roll the vial again and draw the required insulin dose into the syringe. Check for air bubbles in the syringe and verify the administered dose.
- Administer the insulin subcutaneously. How to inject insulin:
- pinch the skin with two fingers, insert the needle under the skin, and inject the syringe contents;
- keep the needle under the skin for 6 seconds, ensuring complete delivery of insulin, then withdraw the needle;
- if bleeding occurs at the injection site after needle removal, press the area firmly with a cotton swab.
For administering Inzuvit® 30/70 from cartridges, use a pen injector according to its detailed user instructions. Before using Inzuvit® 30/70 in cartridges, resuspend the insulin by rolling the cartridge between your palms 10 times and inverting it 180° 10 times until the suspension becomes uniformly cloudy or milky. If the liquid in the cartridge does not achieve the proper appearance, repeat the procedure until the cartridge contents are fully mixed. Regularly check the physical appearance of the cartridge contents; do not use if the suspension contains clumps or if white particles adhere to the bottom or sides of the cartridge, making the glass appear cloudy. Cartridges are not intended for mixing different insulins. Do not refill cartridges. The pen injector is intended for individual use only. Strictly follow the manufacturer's instructions for using the pen injector.
Children.
Inzuvit® 30/70 may be used in children and adolescents.
Overdose.
Although a specific definition of insulin overdose is not established, hypoglycemia may develop in progressive stages if doses exceeding the patient's requirements are administered.
Mild hypoglycemia can be treated by taking glucose or sweet foods orally. Therefore, diabetic patients are advised to always carry several sugar-containing products.
In case of severe hypoglycemia, when the patient is unconscious, individuals who have received appropriate training should administer glucagon subcutaneously or intramuscularly (0.5 to 1.0 mg). A healthcare professional may administer intravenous glucose. Intravenous glucose should also be administered if the patient does not respond to glucagon within 10–15 minutes.
After the patient regains consciousness, carbohydrate-containing food should be administered to prevent recurrence.
Side effects.
The most common adverse effect of therapy is hypoglycaemia. According to clinical trial data and post-marketing surveillance, the incidence of hypoglycaemia varies among different patient groups, dosing regimens, and levels of glycaemic control.
At the beginning of insulin therapy, transient disturbances in refraction, oedema, and injection site reactions (pain, redness, urticaria, inflammation, bruising, swelling, and itching at the injection site) may occur. Rapid improvement in blood glucose control may cause a temporary state of acute painful neuropathy, which is usually reversible. Intensification of insulin therapy aimed at rapid improvement in glycaemic control may lead to transient worsening of diabetic retinopathy; however, long-term, well-established glycaemic control reduces the risk of progression of diabetic retinopathy.
Based on clinical trial data, the adverse reactions listed below are classified by frequency and by system organ class according to MedDRA.
Adverse reactions are categorized by frequency as follows: very common (≥ 1/10), common (≥ 1/100, < 1/10), uncommon (> 1/1000, < 1/100), rare (> 1/10000, < 1/1000), very rare (< 1/10000), and frequency not known (cannot be estimated based on available data).
Immune system disorders:
uncommon – urticaria, rash; very rare – anaphylactic reactions*.
Metabolism and nutrition disorders:
very common – hypoglycaemia*.
Nervous system disorders:
uncommon – peripheral neuropathies (painful neuropathies).
Eye disorders:
uncommon – diabetic retinopathy; very rare – refractive disturbances.
Skin and subcutaneous tissue disorders:
uncommon – lipodystrophy*;
frequency not known – skin amyloidosis.
General disorders and administration site conditions:
uncommon – injection site reactions, oedema.
*See information below.
Selected side effects
Anaphylactic reactions
Symptoms of generalized hypersensitivity (including generalized skin rash, pruritus, sweating, gastrointestinal disturbances, angioedema, dyspnoea, tachycardia, hypotension, and dizziness/loss of consciousness) are very rare but may be potentially life-threatening.
Hypoglycaemia
Hypoglycaemia is the most common adverse effect. It may occur when the insulin dose significantly exceeds the patient's insulin requirements. Severe hypoglycaemia may lead to loss of consciousness, seizures, and subsequent temporary or permanent impairment of brain function, and even to fatal outcome. Symptoms of hypoglycaemia usually appear suddenly. They may include cold sweat, pallor and cold skin, fatigue, nervousness or tremor, anxiety, unusual tiredness or weakness, confusion, difficulty in concentrating, drowsiness, excessive hunger, visual disturbances, headache, nausea, and tachycardia.
Skin and subcutaneous tissue disorders
Lipodystrophy and skin amyloidosis may occur at the injection site and may delay local absorption of insulin. Regular rotation of injection sites within the same body region may help reduce or prevent these reactions (see section "Special instructions").
Paediatric population
Based on post-marketing experience and clinical trial data, the frequency, type, and severity of adverse reactions observed in children do not differ from those in the general population.
Other special populations
Based on post-marketing experience and clinical trial data, the frequency, type, and severity of adverse reactions observed in elderly patients and in patients with renal or hepatic impairment do not differ from those in the general population.
Reporting suspected adverse reactions
It is important to report suspected adverse reactions after marketing authorization of the medicinal product. This allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are encouraged to report suspected adverse reactions to the local pharmacovigilance authorities.
Shelf life. 2 years.
The shelf life of the product in cartridges and vials after first opening is 42 days, stored at a temperature not exceeding 25 ºC, protected from overheating and direct sunlight. Cartridges in use should not be kept in the refrigerator. Do not use the medicinal product after the expiry date stated on the packaging.
Storage conditions.
Store at a temperature between 2 ºC and 8 ºC (in the refrigerator). Do not freeze. Keep out of the reach of children.
Incompatibilities. Insulin suspensions must not be mixed with infusion solutions.
Packaging. 3 ml in a cartridge. 5 cartridges in a blister, 1 blister per pack. 10 ml in a vial. 1 vial per pack.
Prescription status. Prescription only.
Manufacturer. JSC "Farmak".
Manufacturer's address and place of business.
74, Kyrylivska Street, Kyiv, 04080, Ukraine.
Marketing Authorization Holder.
SMARTPHARMA GROUP LLC, Ukraine
Address of Marketing Authorization Holder.
Ukraine, 04116, Kyiv, 26 Peremohy Avenue, office 52
Ukraine, 04116, Kyiv, 26 Peremohy avenue, office 52
Date of last review.