Instructions Sufer solution for intravenous injection 20 mg/ml ampoule 5 ml No. 5
Composition
active ingredient: iron (III) hydroxide sucrose complex;
1 ml of solution contains 20 mg of iron in the form of iron (III) hydroxide sucrose complex;
excipient: water for injections.
Dosage form
Solution for intravenous injection.
Main physicochemical properties: brown aqueous solution.
Pharmacotherapeutic group
Antianemic agents for parenteral administration. Iron preparations. ATC code B03A C.
Pharmacological properties
Pharmacodynamics
Mechanism of action
The active ingredient of the drug Sufer®, iron sucrose, consists of polynuclear iron (III) hydroxide centers surrounded on the outside by a large number of non-covalently bound sucrose molecules. The weight of the complex corresponds to the average molecular weight (Mr), which is approximately 43 kDa. The polynuclear iron center has a structure similar to the structure of the ferritin center, which is a physiological iron-containing protein. The complex is designed in such a way that the absorbed iron is delivered in a controlled manner to the proteins that ensure its transport and storage in the body (transferrin and ferritin, respectively).
After intravenous administration, the multinuclear iron center from the complex is taken up mainly by the reticuloendothelial system of the liver, spleen, and bone marrow. In the second stage, the iron is used for the synthesis of hemoglobin, myoglobin, and other iron-containing enzymes or is stored in the liver as ferritin.
Clinical efficacy
Clinical studies have shown that after intravenous administration of iron (III) hydroxide sucrose complex, the hematological response is observed more quickly than with the use of oral soluble forms of iron.
Pharmacokinetics
Distribution
The ferrokinetics of iron(III) hydroxide sucrose complex labeled with 59Fe and 52Fe were evaluated in 6 patients with anemia and chronic renal failure. During the first 6–8 hours, 52Fe was taken up by the liver, spleen, and bone marrow. It is believed that the uptake of the radiolabel by the macrophage-rich spleen is characteristic of iron uptake by the reticuloendothelial system.
After intravenous administration of a single dose of Sufer® containing 100 mg of iron to healthy volunteers, the maximum iron concentration was observed 10 minutes after administration and reached a mean value of 538 mmol/l. The volume of distribution in the central compartment corresponded to the volume in plasma (approximately 3 liters).
Metabolism
After injection, sucrose is almost completely disintegrated, and the multinuclear iron center is taken up mainly by the reticuloendothelial system of the liver, spleen, and bone marrow.
Within 4 weeks after administration, iron uptake by erythrocytes of 59Fe ranged from 68% to 97%.
Breeding
The average molecular weight of the complex is approximately 43 kDa, which is quite high and does not allow its excretion by the kidneys. Renal excretion of iron during the first 4 hours after injection of 100 mg of iron is less than 5% of the administered dose. Due to
At 24 hours, total serum iron concentration was reduced to baseline (pre-administration) levels, and renal sucrose excretion was approximately 75% of the administered dose.
Pharmacokinetics in specific patient groups
It is not yet known whether renal and hepatic insufficiency affect the pharmacological properties of iron (III) hydroxide sucrose complex (see section "Special instructions").
Indication
Iron deficiency in patients who cannot be prescribed oral iron preparations or in case of their ineffectiveness in the following cases:
- intolerance to oral iron preparations;
- the presence of inflammatory diseases of the gastrointestinal tract (for example, ulcerative colitis), which may be exacerbated by therapy with oral iron preparations;
- iron deficiency states resistant to therapy, in cases where control of these states with oral iron preparations is insufficient.
Sufer® should only be used when the indications are based on appropriate laboratory tests. Appropriate laboratory tests include determination of hemoglobin, serum ferritin, and transferrin iron saturation.
Contraindication
The use of the drug Sufer® is contraindicated in the following conditions:
- hypersensitivity to the active substance or to other components of the drug;
- anemia not associated with iron deficiency (e.g., hemolytic anemia, megaloblastic anemia due to vitamin B12 deficiency, impaired erythropoiesis, bone marrow hypoplasia, anemia caused by lead poisoning);
- iron overload (hemosiderosis, hemochromatosis) or hereditary disorders of iron absorption (for example, sideroachrestic anemia, porphyria cutanea, thalassemia);
- I trimester of pregnancy.
Interaction with other medicinal products and other types of interactions
Sufer® is indicated for patients who cannot be prescribed oral iron preparations due to their intolerance, ineffectiveness, or the presence of gastrointestinal diseases. Sufer® should not be used simultaneously with oral iron preparations, since the absorption of iron administered orally is reduced.
Application features
Parenteral iron preparations may cause immediate-type hypersensitivity reactions, including serious anaphylactic/anaphylactoid reactions, which may be fatal. Such reactions have been reported even in cases where previous use of parenteral iron preparations was uneventful. Hypersensitivity reactions have been reported to progress to Kounis syndrome (acute allergic coronary arteriospasm, which may lead to myocardial infarction, see section 4.8). Sufer® should be used only in cases of extreme necessity, taking all precautions.
Treatment with Sufer® should be prescribed by a doctor only after accurately determining the indication.
Sufer® should only be administered if medical personnel trained in the assessment and treatment of anaphylactic reactions are available for immediate action and in a facility adequately equipped with resuscitation facilities. Before each administration of the medicinal product, the patient should be questioned about previous adverse reactions associated with the use of intravenous iron preparations.
Typical symptoms of immediate-type hypersensitivity reactions are: decreased blood pressure, tachycardia (and even anaphylactic shock), respiratory symptoms (including bronchospasm, laryngeal edema and pharyngeal edema), gastrointestinal symptoms (including abdominal cramps, vomiting) or skin symptoms (including urticaria, erythema, pruritus).
Each patient should be observed for at least 30 minutes after administration of parenteral iron preparations for the timely detection of symptoms of hypersensitivity reactions. If allergic reactions or signs of intolerance occur during the use of the medicinal product, treatment should be discontinued immediately.
For the immediate treatment of acute anaphylactic/anaphylactoid reactions, the first recommended treatment is adrenaline (e.g. 0.3 mg intramuscularly),
then - the use of antihistamines and/or corticosteroids (have a later onset of action).
High risk of hypersensitivity reactions in patients with existing allergies, including drug intolerance, a history of severe bronchial asthma, eczema or other forms of atopy, as well as in patients with immunological and inflammatory diseases (e.g. systemic lupus erythematosus, rheumatoid arthritis).
In patients with hepatic impairment, parenteral iron should be used only after careful benefit-risk assessment. Parenteral iron should be avoided in patients with hepatic impairment when iron overload is a predisposing factor. Close monitoring of iron levels is recommended to avoid overload.
In patients with elevated ferritin levels, parenteral iron preparations may adversely affect the course of bacterial or viral infections.
Parenteral iron preparations should be used with caution in acute or chronic infections. In patients with chronic infections, a benefit/risk assessment should be performed. It is recommended to discontinue Sufer® in patients with bacteremia.
During the administration of the drug, special attention should be paid to avoiding paravenous leakage. Paravenous leakage of the drug may lead to pain, inflammation, tissue necrosis and prolonged brown discoloration of the skin at this site. In the event of paravenous leakage, the drug should be discontinued immediately.
A decrease in blood pressure is commonly observed with the use of intravenous iron preparations. The solution should be administered with caution. The recommendations for the rate of administration of the drug should be strictly followed to prevent the development of arterial hypotension. A higher incidence of undesirable side effects (especially hypotension) is associated with an increase in the dose or rate of administration of the drug.
Special caution should be exercised when using Sufer® in patients with hepatic insufficiency, decompensated cirrhosis, epidemic hepatitis, Randu-Osler-Weber disease, acute infectious kidney diseases, and uncontrolled hyperparathyroidism.
Before use, the ampoule should be inspected for sediment and damage.
Only a brown aqueous solution that does not contain sediment can be used.
Sufer® should be administered immediately after opening the ampoule.
Use during pregnancy or breastfeeding
There are limited data on the use of iron sucrose complex in pregnant women.
I trimester of pregnancy. Data on the use of parenteral iron preparations in pregnant women in the II and III trimesters of pregnancy (303 reports of pregnancy outcomes) showed no adverse effects on the health of the mother and child.
It is not yet known whether iron(III) hydroxide sucrose complex crosses the placenta. Iron bound to transferrin crosses the placental barrier. Iron bound to lactoferrin passes into breast milk.
Studies on the effect on iron levels in newborns have not been conducted.
The drug is contraindicated for use in the first trimester of pregnancy (see the section "Contraindications"). The drug may be used in the second and third trimesters of pregnancy only strictly according to indications.
The benefit/risk ratio should be assessed before using the drug during pregnancy, as hypersensitivity reactions may carry a certain risk for the mother and child (see section "Special warnings and precautions for use").
After parenteral iron administration to a pregnant woman, fetal bradycardia may occur. This condition is usually transient and occurs as a result of a hypersensitivity reaction in the mother. During intravenous administration of iron preparations to pregnant women, the fetus should be carefully monitored.
Pre-pregnancy body weight should be taken into account to calculate the required amount of iron to avoid overdose.
Breastfeeding period
Data on iron excretion in human breast milk after intravenous administration of iron sucrose are limited. In a clinical study, 10 healthy, iron-deficient, breast-feeding women were given 100 mg of iron in the form of a sucrose complex. After four days of treatment, the iron content in breast milk was not increased and did not differ from that in the control group (n = 5). An effect of iron in the mother's breast milk on the newborn/infant cannot be excluded, therefore the benefit/risk ratio should be assessed.
Ability to influence reaction speed when driving vehicles or other mechanisms
There are no relevant studies. The effect on the reaction rate when driving or using other mechanisms is unlikely. However, in the event of adverse reactions such as dizziness, confusion or drowsiness after taking the drug, you should refrain from driving or using other mechanisms until the symptoms disappear.
Method of administration and doses
The drug Sufer® should be administered slowly, intravenously.
The drug is not intended for intramuscular or subcutaneous administration.
Patients should be observed for signs and symptoms of hypersensitivity reactions during and after administration of Sufer®. Appropriate emergency treatment should be provided (see section 4.4).
The total cumulative dose of the drug should be calculated for each patient individually and not exceeded. The dose is calculated taking into account the patient's body weight and hemoglobin level.
In the event that the total required dose exceeds the maximum permitted single dose of 200 mg (for injection) or 500 mg (for infusion), it is recommended to administer the drug in parts.
Dose calculation
The total cumulative dose of Sufer®, equivalent to the total iron deficiency (mg), is determined taking into account the hemoglobin (Hb) level and body weight. The dose is calculated individually according to the total iron deficiency in the patient's body according to the Ganzoni formula:
total iron deficiency (mg) = body weight (kg) x (normal Hb level (g/l) - patient's Hb level (g/l)) ´ 0.24* + stored iron (mg).
For patients with a body weight of less than 35 kg: normal Hb level is 130 g/l, the amount of deposited iron is 15 mg/kg of body weight.
For patients with a body weight of more than 35 kg: normal Hb level is 150 g/l, the amount of deposited iron is 500 mg.
* Coefficient 0.24=0.0034´0.07´1000 (iron content in Hb = 0.34%, blood volume = 7% of body weight, coefficient 1000 = conversion of "g" to "mg").
Total volume of Sufer® to be administered (in ml)
= total iron deficiency (mg)
20 mg/ml
Table 1
Total cumulative dose of Sufer® (ml) to be administered, taking into account the patient's body weight and Hb level:
| Body weight | Total cumulative dose of Sufer® (20 mg iron/ml) for administration |
| (kg) | Hb 60 g/l | Hb 75 g/l | Hb 90 g/l | Hb 105 g/l |
| ml | ml | ml | ml | |
| 10 | 15 | 15 | 12.5 | 10 |
| 15 | 25 | 22.5 | 17.5 | 15 |
| 20 | 32.5 | 27.5 | 25 | 20 |
| 25 | 40 | 35 | 30 | 27.5 |
| 30 | 47.5 | 42.5 | 37.5 | 32.5 |
| 35 | 62.5 | 57.5 | 50 | 45 |
| 40 | 67.5 | 60 | 55 | 47.5 |
| 45 | 75 | 65 | 57.5 | 50 |
| 50 | 80 | 70 | 60 | 52.5 |
| 55 | 85 | 75 | 65 | 55 |
| 60 | 90 | 80 | 67.5 | 57.5 |
| 65 | 95 | 82.5 | 72.5 | 60 |
| 70 | 100 | 87.5 | 75 | 62.5 |
| 75 | 105 | 92.5 | 80 | 65 |
| 80 | 112.5 | 82.5 | 67.5 |
| 85 | 117.5 | 102.5 | 85 | 70 |
| 90 | 122.5 | 107.5 | 90 | 72.5 |
Table 2
The required Hb level depends on the patient's body weight:
| Body weight | Required Hb |
| < 35 kg | 130 g/l |
| ≥ 35 kg | 150 g/l |
To convert Hb (mmol) to Hb (g/L), multiply the first value by 16.
Standard dosage
Adults: 5-10 ml of Sufer® (100-200 mg of iron) 1-3 times a week. For duration of use and dilution factor, see below.
Children over 3 years of age: There are only limited data on the use of the drug in children. In case of clinical need, it is recommended to administer no more than 0.15 ml of Sufer® (3 mg iron) per 1 kg of body weight no more than 3 times a week. For duration of use and dilution factor, see below.
Maximum tolerated single or weekly dose
Adults
For injections, the maximum tolerated dose, administered no more than 3 times a week, is 10 ml of Sufer® (200 mg of iron), the duration of administration is at least 10 minutes.
For infusion, the maximum tolerated dose, administered no more than once a week:
- patients with a body weight of more than 70 kg: 500 mg of iron (25 ml of Sufer®) over at least 3.5 hours;
- patients with a body weight of 70 kg and below: 7 mg of iron per kg of body weight for at least 3.5 hours.
The infusion time should be strictly adhered to, even if the patient does not receive the maximum tolerated single dose.
If there is no improvement in hematological parameters (an increase in hemoglobin level of approximately 1 g/L of blood per day or approximately 10–20 g/L 1–2 weeks after the start of treatment), the patient's initial diagnosis should be reviewed and persistent blood loss should be excluded.
Application
Sufer® can only be administered intravenously by slow injection, drip infusion, or directly into the venous section of the dialysis system.
Sufer® should not be administered intramuscularly or subcutaneously.
If the required total dose exceeds the maximum permissible single dose, the total dose should be divided into several doses.
Intravenous drip
Immediately before administration, the drug Sufer® must be diluted only in sterile 0.9% sodium chloride solution according to the scheme indicated in Table 3.
Table 3
Sufer® dosage (mg iron) | Sufer® dosage (ml) | Maximum volume of sterile 0.9% sodium chloride solution for dilution | Minimum input time |
| 50 mg | 2.5 ml | 50 ml | 8 minutes |
| 100 mg | 5 ml | 100 ml | 15 minutes |
| 200 mg | 10 ml | 200 ml | 30 minutes |
| 300 mg | 15 ml | 300 ml | 1.5 hours |
| 400 mg | 20 ml | 400 ml | 2.5 hours |
| 500 mg | 25 ml | 500 ml | 3.5 hours |
Intravenous jet injection
Sufer® can also be administered intravenously slowly as an undiluted solution at a rate of 1 ml per minute (5 ml of Sufer® (100 mg of iron) is administered in 5 minutes), but the maximum volume of the solution should not exceed 10 ml of Sufer® (200 mg of iron) per injection.
After injection, the patient should straighten the arm. Paravenous leakage of the drug should be avoided, as it may lead to pain, inflammation, tissue necrosis and prolonged brown discoloration of the skin at this site (see section "Special instructions").
Injection into the venous section of the dialysis system
Sufer® can be administered directly into the venous section of the dialysis system during a hemodialysis session, strictly following the rules described for intravenous injection.
Children
Due to insufficient data, the use of Sufer® is not recommended for the treatment of children under 3 years of age.
Overdose
Overdose may lead to acute iron overload, which may manifest as hemosiderosis. In case of overdose, symptomatic treatment and, if necessary, iron-binding agents (chelates) are recommended.
Adverse reactions
The most common adverse reactions in clinical trials were dysgeusia, which occurred at a rate of 4.5 events per 100 people. Other common adverse reactions included nausea, hypotension, hypertension, and infusion site pain, which occurred at a rate of 1 to 2 events per 100 people.
Adverse reactions are classified according to the following frequency: very common (> 1/10), common (> 1/100, < 1/10), uncommon (> 1/1000, < 1/100), rare (> 1/10000, < 1/1000), very rare (1/10000), not known (the available data do not allow an estimate of the frequency, since such events were reported exclusively during post-marketing studies, and not in clinical trials).
On the part of the immune system
Uncommon: hypersensitivity reactions.
Metabolic disorders, metabolism
Uncommon: increased serum ferritin levels.
Neurological disorders
Common: transient taste disturbance, especially metallic taste (dysgeusia), dizziness.
Uncommon: headache, paraesthesia, hypoesthesia.
Rare: loss of consciousness, drowsiness.
Cardiac disorders
Uncommon: hypotension and collapse, tachycardia.
Rare: feeling of palpitations.
Not known: Kounis syndrome.
Vascular disorders
Common: hypotension, hypertension.
Uncommon: feeling hot, phlebitis.
Not known: superficial thrombophlebitis at the injection site.
Respiratory, thoracic and mediastinal disorders
Uncommon: dyspnoea.
From the urinary system
Uncommon: chromaturia.
Gastrointestinal disorders
Common: nausea.
Uncommon: vomiting, abdominal pain, diarrhoea, constipation.
Skin and subcutaneous tissue disorders
Uncommon: itching, rash.
Musculoskeletal and connective tissue disorders
Uncommon: muscle spasms, myalgia, arthralgia, pain in extremity, back pain.
General disorders and administration site conditions
Common: injection/infusion site reactions1.
Uncommon: chest pain, chills, asthenia, fatigue, peripheral oedema, pain.
Rare: increased sweating (hyperhidrosis), fever.
Laboratory indicators
Uncommon: increased levels of alanine aminotransferase, aspartate aminotransferase, gamma-glutamyltransferase.
Rare: increased blood lactate dehydrogenase levels.
1 Most commonly reported: injection/infusion site pain, extravasation, irritation, skin discoloration, haematoma, pruritus.
The following adverse reactions were obtained from spontaneous reports from post-marketing studies:
Frequency unknown: impaired consciousness, bradycardia, thrombophlebitis.
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after the marketing authorisation of a medicinal product is an important procedure. This allows for continued monitoring of the benefit/risk balance of the medicinal product in question. Healthcare professionals should report any suspected adverse reactions through the national pharmacovigilance system.
Expiration date
3 years.
Do not use the drug after the expiration date indicated on the package.
Shelf life after opening the ampoule: From a microbiological point of view, the product should be used immediately.
Shelf life after dilution with saline. Chemical and physical stability after dilution at room temperature is 12 hours.
Storage conditions
Store in a place protected from light. Store at a temperature not exceeding 25 °C.
Do not freeze.
Incompatibility.
Sufer® can only be mixed with sterile 0.9% sodium chloride solution. No other intravenous solutions or therapeutic agents should be added as there is a risk of precipitation and/or other pharmaceutical interactions. Compatibility with polyethylene and polyvinyl chloride containers has not been studied.
Packaging
5 ml glass ampoules No. 5 in a contour blister pack; 1 contour blister pack in a cardboard pack.
Vacation category
According to the recipe.
Producer
LLC "Yuria-Pharm".
Location of the manufacturer and address of its place of business
Ukraine, 18030, Cherkasy region, Cherkasy city, Kobzarska st., 108. Tel.: (044) 281-01-01.
