- The most common prandial analog of ultra-short-acting insulin
- Replacement of proline with aspartic acid
- Faster absorption rate compared to regular human insulin
- In 2020, the share of aspart consumption among prandial insulin analogues in Russia was 56.5 % (DDD)*
This drug is a prescribed medicine. It can be dispensed on a doctor's prescription only. There are contraindications. Please read the patient information leaflet. Do not use the medicinal agent if it was not prescribed by your treating physician. Always follow the patient information leaflet and your doctor’s recommendations.
Composition
1 mL of solution contains:
active ingredient: insulin aspart 100 U (equivalent to 3.5 mg);
excipients: glycerol, phenol, metacresol, zinc (as zinc chloride), sodium chloride, sodium hydrogen phosphate dihydrate, sodium hydroxide and/or hydrochloric acid, water for injection.
One cartridge contains 3 mL of the solution equivalent to 300 IU.
One pre-filled pen injector contains 3 mL of the solution equivalent to 300 IU.
Appearance: Transparent, colourless solution.
Pharmacotherapeutic group of the medicinal product: hypoglycaemic agent, rapid-acting human insulin analogue.
ATC code: А10АB05.
Pharmacological properties
Insulin aspart is a rapid-acting human insulin analogue produced using recombinant DNA biotechnology and Escherichia coli strain with the proline amino acid at position B28 substituted with aspartic acid.
Mechanism of action
The hypoglycaemic effect of insulin aspart is due to increased tissue glucose utilization following insulin binding to muscle and fat cell receptors and a simultaneous reduction in the rate of glucose production by the liver.
Insulin aspart has a faster onset time and reduces blood glucose more significantly in the first 4 hours after a meal than soluble human insulin. Insulin aspart has a shorter duration of action compared to soluble human insulin after subcutaneous injection.
After subcutaneous injection, the onset of action occurs within 10–20 minutes of injection. The maximum effect is exerted between 1 and 3 hours after injection.
The duration of the product action is 3–5 hours.
Pharmacodynamics
Insulin aspart is equipotent to soluble human insulin in molar terms.
Children and adolescents
The use of insulin aspart in children has demonstrated similar results of long-term glycaemic control when compared to soluble human insulin.
A clinical study using soluble human insulin before meals and insulin aspart after meals was conducted in young children (2 to 6 years of age, for 12 weeks); a single-dose PK/PD study was also conducted in children (6–12 years of age) and adolescents (13–17 years of age). The pharmacodynamic profile of insulin aspart in children was similar to that in adult patients.
The efficacy and safety of insulin aspart administered as bolus insulin in combination with insulin detemir or insulin degludec as basal insulin were studied in two 12-month, randomised, controlled clinical studies in children and adolescents aged 1–18 years (n=712).
The improvement in HbA1c and safety profiles were comparable across all age groups.
Adults
Clinical studies in patients with type 1 diabetes mellitus have demonstrated lower postprandial blood glucose with insulin aspart compared to soluble human insulin (see Figure 1).
In two long-term open-label studies involving patients with type 1 diabetes, insulin aspart contributed to decrease of glycated haemoglobin level by 0.12 and 0.15 percentage points compared to soluble human insulin; the difference has limited clinical significance.
Clinical studies in patients with type 1 diabetes mellitus have demonstrated a reduced risk of nocturnal hypoglycaemia with insulin aspart compared to soluble human insulin. The risk of daytime hypoglycaemia was not significantly increased.
Elderly
A randomised, double-blind, crossover pharmacokinetics and pharmacodynamics (PK/PD) study of insulin aspart and soluble human insulin in elderly patients with type 2 diabetes mellitus aged 65–83 years was conducted.
The relative differences in pharmacodynamic properties (GIRmax, AUCGIR, 0–120 min) between insulin aspart and human insulin in elderly patients were similar to those in healthy volunteers and in younger patients with diabetes.
Pregnancy
Clinical studies comparing the safety and efficacy of insulin aspart and human insulin in pregnant women with type 1 diabetes (322 pregnant women studied, of whom 157 received insulin aspart and 165 received soluble human insulin) showed no adverse effects of insulin aspart on pregnancy or foetal/neonatal health.
Additional clinical studies in women with gestational diabetes receiving insulin aspart and human insulin show comparable safety profiles along with a significant improvement in postprandial glucose concentration control with insulin aspart.
Pharmacokinetics
Substitution of the proline amino acid at position B28 with aspartic acid in insulin aspart reduces the tendency of molecules to form hexamers observed in soluble human insulin solution.
Therefore, insulin aspart is absorbed much faster from the subcutaneous fat compared to soluble human insulin.
After subcutaneous injection, the average time to maximum insulin aspart plasma concentration (tmax) is half of that for soluble human insulin. Average maximum plasma concentration (Сmax) amounts to 492±256 pmol/L and is reached 40 (interquartile range: 30–40) minutes after a subcutaneous dose of 0.15 U/kg body weight in patients with type 1 diabetic mellitus. The insulin concentration returns to baseline about 4–6 hours after dosing. The absorption rate is somewhat slower in patients with type 2 diabetes mellitus, resulting in a lower Cmax (352±240 pmol/L) and later tmax (60 (interquartile range: 50–90) minutes). The intra-individual variability in tmax is significantly lower for insulin aspart than for soluble human insulin, whereas the above intra-individual variability in Cmax for insulin aspart is higher.
Special populations
Children and adolescents
Tmax of insulin aspart in children (6–12 years of age) and adolescents (13–17 years of age) with type 1 diabetes mellitus is similar to that in adults. However, Cmax differed between the two age groups, stressing the importance of the individual titration of insulin aspart.
Elderly
A decreased absorption rate was observed in elderly patients, resulting in a later tmax (82 (interquartile range: 60–120) minutes), whereas Cmax was similar to that observed in younger patients with type 2 diabetes mellitus and slightly lower than that in patients with type 1 diabetes mellitus.
Hepatic failure
In patients with hepatic impairment (up to severe), the absorption rate was decreased and was more variable, resulting in delayed tmax from about 50 minutes in subjects with normal hepatic function to about 85 minutes in subjects with moderate to severe hepatic impairment. Other pharmacokinetic parameters were similar in patients with reduced or normal hepatic function.
Renal failure
In patients with renal impairment, no apparent effect of creatinine clearance values on the pharmacokinetic parameters of insulin aspart. Limited data are available for subjects with moderate to severe renal impairment. Patients with renal failure requiring dialysis treatment were not involved in the study.
Authorisation number: ЛП-006600
Trade name: RinFast®.
International non-proprietary name (INN): insulin aspart.
Pharmaceutical form: solution for intravenous and subcutaneous injection.
Composition
1 mL of solution contains:
active ingredient: insulin aspart 100 U (equivalent to 3.5 mg);
excipients: glycerol, phenol, metacresol, zinc (as zinc chloride), sodium chloride, sodium hydrogen phosphate dihydrate, sodium hydroxide and/or hydrochloric acid, water for injection.
One cartridge contains 3 mL of the solution equivalent to 300 IU.
One pre-filled pen injector contains 3 mL of the solution equivalent to 300 IU.
Appearance: Transparent, colourless solution.
Pharmacotherapeutic group of the medicinal product: hypoglycaemic agent, rapid-acting human insulin analogue.
ATC code: А10АB05.
Pharmacological properties
Insulin aspart is a rapid-acting human insulin analogue produced using recombinant DNA biotechnology and Escherichia coli strain with the proline amino acid at position B28 substituted with aspartic acid.
Mechanism of action
The hypoglycaemic effect of insulin aspart is due to increased tissue glucose utilization following insulin binding to muscle and fat cell receptors and a simultaneous reduction in the rate of glucose production by the liver.
Insulin aspart has a faster onset time and reduces blood glucose more significantly in the first 4 hours after a meal than soluble human insulin. Insulin aspart has a shorter duration of action compared to soluble human insulin after subcutaneous injection.
After subcutaneous injection, the onset of action occurs within 10–20 minutes of injection. The maximum effect is exerted between 1 and 3 hours after injection.
The duration of the product action is 3–5 hours.
Pharmacodynamics
Insulin aspart is equipotent to soluble human insulin in molar terms.
Children and adolescents
The use of insulin aspart in children has demonstrated similar results of long-term glycaemic control when compared to soluble human insulin.
A clinical study using soluble human insulin before meals and insulin aspart after meals was conducted in young children (2 to 6 years of age, for 12 weeks); a single-dose PK/PD study was also conducted in children (6–12 years of age) and adolescents (13–17 years of age). The pharmacodynamic profile of insulin aspart in children was similar to that in adult patients.
The efficacy and safety of insulin aspart administered as bolus insulin in combination with insulin detemir or insulin degludec as basal insulin were studied in two 12-month, randomised, controlled clinical studies in children and adolescents aged 1–18 years (n=712).
The improvement in HbA1c and safety profiles were comparable across all age groups.
Adults
Clinical studies in patients with type 1 diabetes mellitus have demonstrated lower postprandial blood glucose with insulin aspart compared to soluble human insulin (see Figure 1).
In two long-term open-label studies involving patients with type 1 diabetes, insulin aspart contributed to decrease of glycated haemoglobin level by 0.12 and 0.15 percentage points compared to soluble human insulin; the difference has limited clinical significance.
Clinical studies in patients with type 1 diabetes mellitus have demonstrated a reduced risk of nocturnal hypoglycaemia with insulin aspart compared to soluble human insulin. The risk of daytime hypoglycaemia was not significantly increased.
Elderly
A randomised, double-blind, crossover pharmacokinetics and pharmacodynamics (PK/PD) study of insulin aspart and soluble human insulin in elderly patients with type 2 diabetes mellitus aged 65–83 years was conducted.
The relative differences in pharmacodynamic properties (GIRmax, AUCGIR, 0–120 min) between insulin aspart and human insulin in elderly patients were similar to those in healthy volunteers and in younger patients with diabetes.
Pregnancy
Clinical studies comparing the safety and efficacy of insulin aspart and human insulin in pregnant women with type 1 diabetes (322 pregnant women studied, of whom 157 received insulin aspart and 165 received soluble human insulin) showed no adverse effects of insulin aspart on pregnancy or foetal/neonatal health.
Additional clinical studies in women with gestational diabetes receiving insulin aspart and human insulin show comparable safety profiles along with a significant improvement in postprandial glucose concentration control with insulin aspart.
Pharmacokinetics
Substitution of the proline amino acid at position B28 with aspartic acid in insulin aspart reduces the tendency of molecules to form hexamers observed in soluble human insulin solution.
Therefore, insulin aspart is absorbed much faster from the subcutaneous fat compared to soluble human insulin.
After subcutaneous injection, the average time to maximum insulin aspart plasma concentration (tmax) is half of that for soluble human insulin. Average maximum plasma concentration (Сmax) amounts to 492±256 pmol/L and is reached 40 (interquartile range: 30–40) minutes after a subcutaneous dose of 0.15 U/kg body weight in patients with type 1 diabetic mellitus. The insulin concentration returns to baseline about 4–6 hours after dosing. The absorption rate is somewhat slower in patients with type 2 diabetes mellitus, resulting in a lower Cmax (352±240 pmol/L) and later tmax (60 (interquartile range: 50–90) minutes). The intra-individual variability in tmax is significantly lower for insulin aspart than for soluble human insulin, whereas the above intra-individual variability in Cmax for insulin aspart is higher.
Special populations
Children and adolescents
Tmax of insulin aspart in children (6–12 years of age) and adolescents (13–17 years of age) with type 1 diabetes mellitus is similar to that in adults. However, Cmax differed between the two age groups, stressing the importance of the individual titration of insulin aspart.
Elderly
A decreased absorption rate was observed in elderly patients, resulting in a later tmax (82 (interquartile range: 60–120) minutes), whereas Cmax was similar to that observed in younger patients with type 2 diabetes mellitus and slightly lower than that in patients with type 1 diabetes mellitus.
Hepatic failure
In patients with hepatic impairment (up to severe), the absorption rate was decreased and was more variable, resulting in delayed tmax from about 50 minutes in subjects with normal hepatic function to about 85 minutes in subjects with moderate to severe hepatic impairment. Other pharmacokinetic parameters were similar in patients with reduced or normal hepatic function.
Renal failure
In patients with renal impairment, no apparent effect of creatinine clearance values on the pharmacokinetic parameters of insulin aspart. Limited data are available for subjects with moderate to severe renal impairment. Patients with renal failure requiring dialysis treatment were not involved in the study.
Indications
Diabetes mellitus in adults, adolescents and children aged 1 year and above.
Contraindications
Hypersensitivity to insulin aspart or to any of the product excipients.
RinFast® is not recommended in children under 1 year of age, since no clinical studies have been conducted in children under 1 year.
Use during pregnancy and lactation
Pregnancy
RinFast® (insulin aspart) can be used during pregnancy. Data from two randomised controlled clinical studies (322 + 27 examined pregnant women) do not indicate any adverse effect of insulin aspart on pregnancy or on the health of the foetus/newborn when compared to soluble human insulin (see the “Pharmacological properties” section).
Close monitoring of blood glucose levels and monitoring of pregnant women with diabetes mellitus (type 1, type 2, or gestational diabetes mellitus) are recommended throughout pregnancy and during possible pregnancy. Insulin requirements generally decrease during the first trimester and gradually increase during the second and third trimesters of pregnancy. Insulin requirements quickly return to pre-pregnancy levels after delivery.
Lactation
RinFast® can be used during breastfeeding, as the use of insulin during breastfeeding does not pose a threat to the baby.
However, dose adjustments of RinFast® may be required.
Posology and method of administration
Doses
The dose of RinFast® is determined by the physician individually, in accordance with the needs of the patient. The product is generally used in combination with intermediate-acting or long-acting insulin products injected at least once a day.
RinFast® can also be used for continuous subcutaneous insulin infusions (CSSIs) in insulin pumps or administered intravenously by medical personnel. To achieve optimal glycaemic control, regular blood glucose measurement and insulin dose adjustment are recommended.
Usually, the individual daily requirements in insulin in adults and children are 0.5 to 1 U/kg of body weight.
Injection therapy: In basal-bolus therapy, 50–70 % of insulin requirements can be covered with RinFast®, while the remaining insulin requirements (30–50 %) are managed with intermediate- or long-acting insulin.
Continuous subcutaneous insulin infusions (CSSIs): RinFast® can be used for CSSIs in insulin pumps as monotherapy only. In this case, RinFast® will cover both bolus (50–70 %) and basal insulin (30–50 %) requirements. An increased patient’s physical activity, a change in the usual diet, or concomitant diseases may lead to the need for dose adjustment.
RinFast® has a faster onset and shorter duration of action than soluble human insulin.
Due to the shorter duration of action compared to human insulin, the risk of developing nocturnal hypoglycaemia in patients receiving RinFast® is lower.
Special populations
As with other insulin products, in elderly patients and in patients with renal or hepatic impairment, blood glucose monitoring should be intensified and the insulin aspart dose adjusted on an individual basis.
Children and adolescents
RinFast® can be used in children and adolescents aged 1 year and above in preference to soluble human insulin when a rapid onset of action might be beneficial, for example, in the timing of the injections in relation to meals (see the “Pharmacological properties” section).
The safety and efficacy of insulin aspart in children below 1 year of age have not been established. No data are available.
Transfer from other insulin products
When transferring from other insulin products, adjustment of the RinFast® dose and the dose of basal insulin may be necessary.
Method of administration
RinFast® is a rapid-acting insulin analogue.
RinFast® is injected subcutaneously in the anterior abdominal wall, thigh, shoulder, deltoid, or buttock region. Injection sites should always be rotated within the same region in order to reduce the risk of lipodystrophy.
As with all insulin products, subcutaneous injection into the anterior abdominal wall ensures a faster absorption than other injection sites.
The duration of action varies according to the dose, injection site, blood flow, temperature and level of physical activity. Nevertheless, the faster onset of action compared to soluble human insulin is maintained regardless of the injection site.
Due to a faster onset of action, RinFast® should be taken by a patient immediately before meals or, if needed, immediately after a meal.
Use of RinFast® cartridges with reusable pen injectors
RinFast® cartridges may be used with reusable pen injectors:
• HumaPen® Savvio insulin pen-injector (Eli Lilly and Company, USA)
• RinsaPen® I individual insulin pen-injector with accessories (Ypsomed AG, Switzerland)
• RinsaPen® II individual insulin pen-injector with accessories (Ypsomed AG, Switzerland)
These cartridges should not be used with other reusable pen injectors; dose accuracy has been validated when used with above pen injectors only. Before using the selected pen injector, please read the manufacturer’s manual for use of reusable pen injectors supplied with each pen injector.
Continuous subcutaneous insulin infusions (CSSIs): RinFast® can be used for CSSIs in insulin pumps designed for insulin infusions. CSSIs should be performed into the anterior abdominal wall. Infusion sites should be rotated periodically.
When used with an insulin infusion pump for subcutaneous injection, RinFast® should not be mixed with any other medicinal products.
Intravenous administration:
If necessary, RinFast® may be administered intravenously, but only by qualified health professionals.
For intravenous use, infusion systems with RinFast® 100 U/mL at concentrations 0.05 U/mL to 1 U/mL insulin aspart are used in the following infusion fluids: 0.9 % sodium chloride solution, 5 % dextrose solution or 10 % dextrose solution containing 40 mmol/L potassium chloride, using polypropylene infusion containers.
These solutions are stable at room temperature for 24 hours.
Although stable over time, a certain amount of insulin will initially be absorbed to the material of the infusion system. Constant monitoring of blood glucose is necessary during the infusion.
Directions for use of RinFast®
Protect from excessive heat and light.
When storing cartridges and pre-filled multidose disposable pen injectors for multiple injections Rinastra® II in a refrigerator, care should be taken to ensure that containers do not come into direct contact with the freezing compartment or frozen packs.
Before the first use, cartridges and pre-filled multidose disposable pen injectors for multiple injections Rinastra® II should be kept at room temperature for 1–2 hours. Do not keep Rinastra® II pen injector when used in a refrigerator.
Do not keep opened cartridges with the medicinal product and the pen injector when used or carried as a spare in a refrigerator. Store at a temperature below 30 °C.
Use within 4 weeks.
Keep the pen cap on in order to protect from light.
Side effects
Adverse reactions observed in patients using RinFast® are mostly caused by the pharmacological effect of insulin.
The most common side effect reported during treatment is hypoglycaemia. The rate of hypoglycaemia varies depending on the patient population, dosage regimen and glycaemic control (see the “Description of selected adverse reactions” section).
At the initial stage of insulin therapy, refractive errors, oedema, and other reactions may occur at the injection sites (pain, redness, urticaria, inflammation, haematoma, swelling, and itching at the injection site). These symptoms are usually transient.
Rapid improvement in glycaemic control can lead to a state of acute pain neuropathy, which is usually reversible. The intensification of insulin therapy with a sharp improvement in carbohydrate metabolism control can lead to a temporary worsening of diabetic retinopathy, while long-term improvement in glycaemic control reduces the risk of diabetic retinopathy advance.
The list of adverse reactions presented in the table and based on clinical trial data is divided into groups as per the rate of adverse reactions in accordance with MedDRA and organ systems. The incidence rate of adverse reactions is defined as: very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1000 to <1/100); rare (≥1/10000 to <1/1000); very rare (<1/10000), and unknown (cannot be assessed based on available data).
- Immune system disorders: Uncommon: urticaria, skin rash, eruption; Very rare: anaphylactic reactions*.
- Metabolism and nutrition disorders: Very common: hypoglycaemia*.
- Nervous system disorders: Rare: peripheral neuropathy (“acute pain neuropathy”).
- Eye disorders: Uncommon: refraction disorders; Uncommon: diabetic retinopathy.
- Skin and subcutaneous tissue disorders: Uncommon: lipodystrophy*.
- General disorders and administration site conditions: Uncommon: injection site reactions; Uncommon: oedema.
Description of selected adverse reactions
Anaphylactic reactions
Very rare reactions of generalised hypersensitivity, which are potentially life-threatening, are reported (including generalised skin rash, itching, increased sweating, gastrointestinal upset, angioedema, respiratory difficulty, rapid heartbeat, decreased blood pressure).
Hypoglycaemia
Hypoglycaemia is the most common adverse event. It may develop if the insulin dose is too high in relation to the insulin requirement. Severe hypoglycaemia can lead to loss of consciousness, and/or spasms, temporary or irreversible impairment of brain function, and, in some cases, to death.
Symptoms of hypoglycaemia usually occur suddenly. These symptoms may include cold sweats, skin pallor, increased fatigue, nervousness or shivering, anxiety, unusual fatigue or weakness, disorientation, impaired concentration, drowsiness, a strong feeling of hunger, visual impairment, headache, nausea, and rapid heartbeat.
Clinical studies have revealed that the incidence rate of hypoglycaemia varies depending on the patient population, dosage regimen, and glycaemic control. According to clinical studies, no difference was identified in the overall rate of hypoglycaemia episodes, when comparing the patients receiving aspart insulin therapy and the patients using human insulin products.
Lipodystrophy
Lipodystrophy (including lipohypertrophy, lipoatrophy) may occur at the injection site. Rotation of the injection site within the given injection area reduces the risk of this adverse reaction.
Overdose
No specific dose required for insulin overdose has been established, however, hypoglycaemia may develop over sequential stages if too high doses relative to the patient’s requirement are administered.
• Mild hypoglycaemic episodes can be treated by the patient by oral administration of glucose or sugary products. It is therefore recommended that the diabetic patient always carries sugar-containing products.
• Severe hypoglycaemic episodes, where the patient has become unconscious, can be treated with glucagon (0.5 to 1 mg) given intramuscularly or subcutaneously (can be administered by a trained person), or with dextrose (glucose) solution given intravenously (can only be administered by healthcare staff). Dextrose should also be given intravenously, if the patient does not regain consciousness within 10–15 minutes after glucagon administration. After the recovery of consciousness, the patient should take a carbohydrate-rich meal to prevent recurrent hypoglycaemia.
Interaction with other medicinal products
A number of medicinal products are known to interact with the glucose metabolism.
The following substances may reduce the patient’s insulin requirements:
Oral antidiabetic medicinal products, monoamine oxidase inhibitors (MAOI), non-selective beta-adrenoblockers, angiotensin converting enzyme (ACE) inhibitors, salicylates, anabolic steroids and sulphonamides.
The following substances may increase the patient’s insulin requirements:
Oral hormonal contraceptives, thiazide diuretics, glucocorticosteroids, thyroid hormones, sympathomimetics, somatropin and danazol.
Beta-adrenoblockers may mask the symptoms of hypoglycaemia.
Octreotide/lanreotide may either increase or decrease the insulin requirement.
Ethanol (alcohol) may intensify or reduce the hypoglycaemic effect of insulin.
Incompatibilities
Some medicinal products may cause degradation of insulin aspart when added to RinFast®.
RinFast® should not be mixed with other medicinal products except for mixing with insulin isophane in a syringe for subcutaneous use, or with solutions for infusion as described in the “Posology and method of administration” section.
Special precautions
Before a long trip through different time zones, the patient should seek the doctor’s advice since this may mean that the patient has to take the insulin and meals at different times.
Hyperglycaemia
Inadequate dosing or discontinuation of treatment, especially in type 1 diabetes, may lead to hyperglycaemia and diabetic ketoacidosis.
Usually, the symptoms of hyperglycaemia develop gradually over a period of hours or days. They include thirst, increased frequency of urination, nausea, vomiting, drowsiness, flushed dry skin, dry mouth, loss of appetite as well as acetone odour of breath. In type 1 diabetes, untreated hyperglycaemia eventually lead to diabetic ketoacidosis, which is potentially lethal.
Hypoglycaemia
Omission of a meal or unplanned, strenuous physical exercise may lead to hypoglycaemia.In children, care should be taken to match insulin doses (especially in basal-bolus regimens) with food intake, physical activities and blood glucose level in order to minimise the risk of hypoglycaemia.
Hypoglycaemia may occur if the insulin dose is too high in relation to the insulin requirement (see the “Side effects” and “Overdose” sections).
After compensation of carbohydrate metabolism (e. g. by intensified insulin therapy), patients may experience a change in their usual warning symptoms of hypoglycaemia, and should be advised accordingly. Usual warning symptoms may disappear in patients with longstanding diabetes.
A consequence of pharmacodynamic characteristics of rapid-acting insulin analogues is that hypoglycaemia may occur earlier during their use when compared with soluble human insulin.
Since RinFast® should be administered in immediate relation to a meal, the rapid onset of action should be considered in patients with concomitant diseases or treatment where a delayed absorption of food might be expected.
Concomitant illness, especially infections and feverish conditions, usually increases the patient’s insulin requirements. Dose adjustments may also be required in patients with concomitant diseases of the kidneys, liver or diseases affecting the adrenal, pituitary or thyroid glands.
When the patients are transferred to other types of insulin, the early warning symptoms of hypoglycaemia may become less pronounced than those experienced with their previous insulin.
Transfer from other insulin medicinal products
Transferring a patient to a new type of insulin or insulin from another manufacturer should be done under strict medical supervision. Changes in strength, manufacturer, type, origin (human insulin, human insulin analogue) and/or method of manufacture may result in the need for dose adjustments. Patients transferred to RinFast® from another type of insulin may require a change in dose from that used with their previous insulin medicinal products. Dose adjustment may be done with the first dose or during the first few weeks or months of treatment.
Injection site reactions
As with other insulin products, injection site reactions may occur and include pain, redness, hives, inflammation, bruising, swelling and itching. Regular rotation of the injection site within a given area reduces the risk of developing these reactions. The reactions typically resolve in a few days to a few weeks. On rare occasions, injection site reactions may require discontinuation of RinFast®.
Concomitant use of thiazolidinediones and insulin products
Cases of chronic cardiac failure have been reported when thiazolidinediones were used in combination with insulin products, especially in patients with risk factors for development of chronic cardiac heart failure. This should be kept in mind if treatment with the combination of thiazolidinediones and insulin products is considered. If the combination therapy is prescribed, patients should be observed for signs and symptoms of chronic heart failure, weight gain and oedema. Thiazolidinediones should be discontinued if any deterioration in cardiac symptoms occurs.
Avoidance of accidental mix-ups of insulin products
Patients must be instructed to always check the insulin label before each injection to avoid accidental mix-ups between RinFast® and other insulin products.
Insulin antibodies
Insulin administration may cause insulin antibodies to form. In rare cases, the presence of insulin antibodies may necessitate adjustment of the insulin dose in order to prevent occurrence of hyper- or hypoglycaemia.
Effects on ability to drive or operate machinery
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 while driving a car or operating machinery. This is particularly important in those patients who have absent or diminished warning symptoms of hypoglycaemia or have frequent episodes of hypoglycaemia. The advisability of driving or performing similar activities should be considered in these circumstances.
Dosage form
Solution for intravenous and subcutaneous injection, 100 U/mL.
3 mL of the medicinal product in clear neutral glass cartridges with rubber plungers, sealed with flip-off aluminium caps with rubber discs.
A label made of transparent polypropylene film is applied to each cartridge.
5 cartridges in blisters of polyvinylchloride or polyethylene terephthalate film and aluminium foil. 1 blister with a package leaflet into a carton.
The cartridge is placed into plastic multidose disposable pen injector for multiple injections Rinastra® II. A label made of polypropylene film is applied to the body of each pen injector.
5 pre-filled multidose disposable pen injectors for multiple injections Rinastra® II with a package leaflet and a user’s manual into a carton.
Storage conditions
For RinFast® in cartridges
Keep out of reach of children.
Store at 2°C to 8°C (in refrigerator), but not near the freezer compartment. Do not freeze. RinFast® should be protected from excessive heat and light.
Cartridges should be stored in a carton to protect from light.
Do not keep opened cartridges with the medicinal product in a refrigerator. Store at a temperature below 30 °C. Use within 4 weeks.
Keep out of reach of children.
Store at 2°C to 8°C (in refrigerator), but not near the freezer compartment. Do not freeze.
RinFast® should be protected from excessive heat and light.
Keep the pen cap on in order to protect from light.
Do not keep Rinastra® II pen injector when used or carried as a spare in a refrigerator. Store at a temperature below 30 °C.
Use within 4 weeks.
Shelf life
30 months.
Do not use after the expiration date indicated on the package.
Prescription status
Prescription only.
Marketing authorisation owner/holder
ООО “GEROPHARM”, Russia
9, ul. Zvenigorodskaya, St. Petersburg, 191119
Phone: (812) 703-79-75 (multiline), fax: (812) 703-79-76
Manufacturer
ООО “GEROPHARM”, Russia
Manufacturing site address:
Bldg. 5, “Kvartal A” area, Obolensk work settlement, Serpukhov city district, Moscow region, 142279, Russia
Unit 1, bldg. 5, “Kvartal A” area, Obolensk work settlement, Serpukhov city district, Moscow region, 142279, Russia
Unit 82, bldg. 4, “Kvartal A” area, Obolensk work settlement, Serpukhov city district, Moscow region, 142279, Russia
Organisation accepting customer complaints
ООО “GEROPHARM”
11B, Degtyarny per., Saint Petersburg, 191144, Russia
Phone: (812) 703-79-75 (multi-line)
Fax: (812) 703-79-76
Hotline number: 8-800-333-4376 (free throughout Russia)
Please send any information on adverse reactions to
farmakonadzor@geropharm.com or using the above contact information of ООО “GEROPHARM”
Solutions relating the package should provide safety and control when using insulin.
The package has several types of informational indications.
The informational indications are visual (colorful, numeral) and tactile – for patients with poor eyesight.
Color indication
Color indication of Rinsulin type is given in accordance with IDF color chart (International Diabetes Federation).
For Rinsuin NPH this is a light-green strip on the package and on the cartridge. If the cartridge is already mounted into RinAstra NPH pen, the button for dose administration of such pen is light-green with two light-green strips at the label of the pen case.
For Rinsuin R this is a yellow strip on the package and on the cartridge. If the cartridge is already mounted into RinAstra R pen, the button for dose administration of such pen is yellow with two yellow strips at the label of the pen case.
Numeral indication
Numeral indication of Rinsulin type is given as QR code. QR (Quick Response) is a barcode giving information for fast recognition thereof with the help of the mobile phone’s camera. QR code scanned this way directs a doctor or a patient to the website of GEROPHARM to the page about Rinsulin®.
Tactile indication
Tactile indication of Rinsulin type is given as a convex indication (Braille). So the package is suitable for people with poor eyesight.
Safety
Patient safety when using different types and packages of Rinsulin can be of several levels:
• control of the first opening of the package in the form of a valve;
• free edge of the foil for easy removal of the cartridge of Rinsulin;
• all the surfaces of a blister with Rinsulin cartridges are rounded without sharp edges. This is significant for patients with diabetes mellitus who can have reduced sensitivity and they can damage their skin without noticing and feeling pain.
