Iron hydroxide sucrose complex trade name. Likferr (iron - hydroxide sucrose complex) - a new domestic iron preparation for parenteral administration

solution for intravenous administration

Each ampoule contains:

active substance: iron hydroxide concentrate of sucrose complex in an amount equivalent to 100 mg of iron;

Excipients: sodium hydroxide - to regulate pH to a value from 10.9 to 11.1, water for injection - up to 5 ml.

Dark brown colloidal solution.

The polynuclear iron(III) hydroxide centers are surrounded on the outside by many non-covalently bound sucrose molecules. As a result, a complex is formed, the molecular weight of which is approximately 43 kDa, as a result of which its excretion through the kidneys in unchanged form is impossible. This complex is stable and does not release iron ions under physiological conditions. The structure of the multinuclear iron-containing core is similar to the structure of the ferritin core, a physiological iron depot. This complex is designed to create a controlled source of utilized iron for transferrin and ferritin, which are responsible for the transport and storage of iron in the body.

After intravenous administration, iron from this complex is taken up primarily by the liver, spleen and bone marrow and is then used for the synthesis of hemoglobin, myoglobin and other iron-containing enzymes, or stored in the liver in the form of ferritin.

After a single intravenous administration of the drug Iron hydroxide sucrose complex containing 100 mg of iron, the maximum concentration of iron, on average 538 μmol, is achieved 10 minutes after injection. The volume of distribution of the central chamber almost completely corresponds to the volume of serum (about 3 l).

The half-life is about 6 hours. The volume of distribution at steady state is approximately 8 liters, which indicates a low distribution of iron in body fluids. Due to the low stability of iron sucrose in comparison with transferrin, there is a competitive exchange of iron in favor of transferrin and as a result, in 24 About 31 mg of iron is transferred per hour.

Iron excretion by the kidneys during the first 4 hours after injection is less than 5% of the total clearance. After 24 hours, the serum iron level returns to its original (pre-administration) value, and approximately 75% of sucrose leaves the vascular bed.

Iron hydroxide sucrose complex is used to treat iron deficiency conditions in the following cases:

• if you need to quickly replenish iron;
• in patients who cannot tolerate oral iron supplements or do not comply with treatment regimen;
• in the presence of active inflammatory bowel diseases, when oral iron supplements are ineffective.

The use of the drug Iron hydroxide sucrose complex is contraindicated if:

• anemia is not associated with iron deficiency;
• there are signs of iron overload (hemosiderosis, hemochromatosis) or a violation of the process of its utilization;
• there is hypersensitivity to the drug Iron hydroxide sucrose complex or its components;
• I trimester of pregnancy.

Patients with bronchial asthma, eczema, polyvalent allergies, allergic reactions to other parenteral iron preparations and persons with low serum iron-binding capacity and/or folic acid deficiency should be prescribed Iron hydroxide sucrose complex with caution.

Caution is also required when administering iron supplements to patients with liver failure, acute or chronic infectious diseases, and individuals with elevated serum ferritin levels due to the fact that parenterally administered iron may have an adverse effect in the presence of a bacterial or viral infection.

Limited experience with the use of the drug Iron hydroxide sucrose complex in pregnant patients has shown the absence of undesirable effects of iron sucrose on the course of pregnancy and the health of the fetus/newborn. To date, there have been no well-controlled studies in pregnant women. Animal reproduction studies have shown no direct or indirect harmful effects on embryo/fetal development, parturition or postnatal development. However, an assessment of the risk/benefit ratio is required.

It is unlikely that unmetabolized iron sucrose passes into breast milk. Therefore, Iron hydroxide sucrose complex does not pose a risk to breastfed infants.

Introduction: Iron hydroxide sucrose complex is administered only intravenously - slowly in a stream or drip, as well as into the venous section of the dialysis system and is not intended for intramuscular administration. Simultaneous administration of the full therapeutic dose of the drug is unacceptable.

Before administering the first therapeutic dose, it is necessary to prescribe a test dose. If during the observation period phenomena of intolerance occur, administration of the drug should be stopped immediately. Before opening, the ampoule must be inspected for possible sediment and damage. Only brown solution without sediment can be used.

Drip administration: It is preferable to administer the drug Iron hydroxide sucrose complex during a drip infusion in order to reduce the risk of a pronounced decrease in blood pressure (BP) and the risk of the solution entering the perivenous space. Immediately before infusion, the drug Iron hydroxide sucrose complex should be diluted with 0.9% sodium chloride solution in a ratio of 1:20 [for example, 1 ml (20 mg of iron) in 20 ml of 0.9% sodium chloride solution]. The resulting solution is administered at the following speed: 100 mg of iron - no less than 15 minutes; 200 mg of iron - within 30 minutes; 300 mg of iron - for 1.5 hours; 400 mg of iron - for 2.5 hours; 500 mg of iron - over 3.5 hours. The maximum tolerated single dose of 7 mg iron/kg body weight should be administered over a minimum of 3.5 hours, regardless of the total dose of the drug.

Before the first drip administration of a therapeutic dose of the drug Iron hydroxide sucrose complex, it is necessary to administer a test dose: 20 mg of iron for adults and children weighing more than 14 kg and half the daily dose (1.5 mg iron/kg) for children weighing less than 14 kg, in for 15 minutes. In the absence of adverse events, the remainder of the solution should be administered at the recommended rate.

Jet introduction: The drug Iron hydroxide sucrose complex can also be administered as an undiluted solution intravenously slowly, at a rate (norm) of 1 ml of the drug Iron hydroxide sucrose complex (20 mg iron) per minute (5 ml of the drug Iron hydroxide sucrose complex (100 mg iron) is administered at least in 5 minutes). The maximum volume of the drug should not exceed 10 ml of the drug Iron hydroxide sucrose complex (200 mg of iron) per injection.

Before the first jet injection of a therapeutic dose of the drug Iron hydroxide sucrose complex, a test dose should be prescribed: 1 ml of the drug Iron hydroxide sucrose complex (20 mg iron) for adults and children weighing more than 14 kg, and half the daily dose (1.5 mg iron /kg) for children with body weight less than 14 kg for 1-2 minutes. If there are no adverse events during the next 15 minutes of observation, the remainder of the solution should be administered at the recommended rate. After the injection, the patient is recommended to fix his arm in an extended position for a while.

Introduction to Dialysis System: Iron hydroxide sucrose complex can be administered directly into the venous portion of the dialysis system, strictly following the rules described for intravenous injection.

Dose calculation: The dose is calculated individually in accordance with the general iron deficiency in the body using the formula:

General iron deficiency (mg) = body weight (kg) x (normal Hb level - patient's Hb) (g/l) x 0.24* + deposited iron (mg).

For patients with body weight less than 35 kg: normal Hb level = 130 g/l, amount of deposited iron = 15 mg/kg body weight.

For patients weighing more than 35 kg: normal Hb level = 150 g/l, amount of deposited iron = 500 mg.

* Coefficient 0.24 = 0.0034 x 0.07 x 1000 (Iron content in Hb = 0.34%; Blood volume = 7% of body weight; coefficient 1000 = conversion of “g” to “mg”).

Total volume of Iron hydroxide sucrose complex to be administered (in ml) = Total iron deficiency (mg) / 20 mg/ml.

In cases where the total therapeutic dose exceeds the maximum permissible single dose, split administration of the drug is recommended.

If, 1-2 weeks after the start of treatment with Iron hydroxide sucrose complex, there is no improvement in hematological parameters, it is necessary to reconsider the initial diagnosis.

Calculation of the dose to replenish iron deficiency after blood loss or donation of autologous blood:

The dose of the drug Iron hydroxide sucrose complex required to compensate for iron deficiency is calculated using the following formula:

If the amount of blood lost is known: intravenous administration of 200 mg of iron (= 10 ml of the drug Iron hydroxide sucrose complex) leads to the same increase in Hb concentration as the transfusion of 1 unit of blood (= 400 ml with an Hb concentration of 150 g/l).

Amount of iron to be replaced (mg) = units of blood lost x 200 OR

Required volume of the drug Iron hydroxide sucrose complex (ml) =

number of units of blood lost x 10

When decreasingHb: use the previous formula provided that iron depots do not need to be replenished.

The amount of iron that needs to be replenished [mg] = body weight [kg] x 0.24 x (normal Hb level - patient’s Hb level) (g/l),

For example: body weight 60 kg, Hb deficiency = 10 g/l => required amount of iron 150 mg => required volume of the drug Iron hydroxide sucrose complex = 7.5 ml

Standard dosage:

Adults and elderly patients: 5-10 ml Iron hydroxide sucrose complex (100-200 mg iron) 1-3 times a week depending on hemoglobin level.

Children: There are only limited data on the use of the drug in children under 3 years of age. The recommended dose for children of other age groups is no more than 0.15 ml of the drug Iron hydroxide sucrose complex (3 mg of iron) per kg of body weight 1-3 times a week, depending on the hemoglobin level.

Maximum tolerated single dose:

Adults and elderly patients:

For jet injection: 10 ml of the drug Iron hydroxide sucrose complex (200 mg of iron), duration of administration of at least 10 minutes.

For drip administration: depending on the indications, a single dose can reach 500 mg of iron. The maximum permissible single dose is 7 mg of iron per kg of body weight and is administered once a week, but it should not exceed 500 mg of iron. For the time of administration of the drug and the method of dilution, see the section "Methods of administration and doses".

The most frequently reported adverse drug reactions when using Iron hydroxide sucrose complex preparations were changes in taste, decreased blood pressure, pyrexia and chills, reactions at the injection site and nausea.

Very common (> 1/10), frequent (> 1/100 -<1/10), нечастые (>1/1000-< 1/100), редкие (>1/10000 - <1/100), очень редкие (< 1/10000), частота неизвестна (оценка их частоты по имеющимся данным невозможна).

From the immune system

Rare: anaphylactoid reactions.

From the nervous system

Frequent: taste disturbances. Uncommon: dizziness, headache. Rare: paresthesia, fainting, loss of consciousness, burning sensation. Frequency unknown: decreased levels of consciousness, confusion.

From the side of the heart

Uncommon: tachycardia, palpitations. Unknown: bradycardia.

From the side of blood vessels

Uncommon: decreased blood pressure. vascular collapse. Rare: increased blood pressure.

From the respiratory system, chest cavity and mediastinum

Uncommon: bronchospasm, shortness of breath.

From the gastrointestinal tract

Uncommon: nausea, vomiting, abdominal pain, diarrhea.

From the skin and subcutaneous tissues

Uncommon: pruritus, urticaria, rash, erythema

From the musculoskeletal system and connective tissue

Uncommon: muscle spasms, muscle pain.

Rare: joint swelling, joint pain.

General disorders and reactions at the injection site

Uncommon: pyrexia, chills, hot flashes, labor pain, injection site reactions (eg, superficial phlebitis and edema). Rare: angioedema, peripheral edema, fatigue, asthenia, general malaise, feeling of heat, edema. Very rare: hyperhidrosis, back pain. Unknown: Chromaturia.

Overdose can cause acute iron overload, which manifests itself as symptoms of hemosiderosis. In case of overdose, it is recommended to use symptomatic agents and, if necessary, substances that bind iron (chelates), for example, intravenously.

Iron hydroxide sucrose complex should not be prescribed simultaneously with dosage forms of iron for oral administration, as it helps to reduce the absorption of iron from the gastrointestinal tract. Treatment with oral iron supplements can be started no earlier than 5 days after the last injection.

The drug Iron hydroxide sucrose complex can be mixed in one syringe only with a sterile 0.9% sodium chloride solution. Incompatible with other intravenous solutions and therapeutic drugs due to the risk of precipitation and/or other pharmaceutical interactions. Compatibility with containers made of other materials (polyethylene and polyvinyl chloride), with the exception of glass, has not been studied.

Iron hydroxide sucrose complex should be prescribed only to those patients in whom the diagnosis of anemia is confirmed by appropriate laboratory data (for example, the results of determining serum ferritin or hemoglobin and hematocrit levels, the number of erythrocytes and their parameters - the average volume of an erythrocyte, the average content, hemoglobin in an erythrocyte or the average: hemoglobin concentration in the erythrocyte).

Intravenous iron supplements may cause allergic or anaphylactoid reactions, which can be potentially life-threatening.

The rate of administration of the drug Iron hydroxide sucrose complex should be strictly observed (with rapid administration of the drug, blood pressure may decrease). A higher incidence of undesirable side effects (especially lowering blood pressure), which can also be severe, is associated with an increase in dose. Thus, the dosage and administration times given in the Dosage and Administration section must be strictly followed, even if the patient is not receiving the maximum tolerated single dose.

Studies conducted in patients with hypersensitivity reactions to iron dextran showed the absence of complications during treatment with iron hydroxide sucrose complex preparations.

Penetration of the drug into the perivenous space should be avoided, because If the drug Iron hydroxide sucrose complex enters the vessel, it leads to tissue necrosis and brown discoloration of the skin. If this complication develops, to accelerate the removal of iron and prevent its further penetration into surrounding tissues, it is recommended to apply heparin-containing drugs to the injection site (gel or ointment is applied with light movements, without rubbing).

Shelf life after first opening the container: From a microbiological point of view, the drug should be used immediately.

It is unlikely that the drug Iron hydroxide sucrose complex may have an undesirable effect on the ability to drive a car and use machinery. However, if symptoms such as dizziness, confusion or fainting develop, patients should not drive vehicles or operate machinery until these symptoms disappear.

Solution for intravenous administration 20 mg/ml.

5 ml in dark glass ampoules with a break ring or a notch and a dot.

5 ampoules in a plastic tray.

1 plastic tray along with instructions for use is placed in a cardboard pack.

In a place protected from direct sunlight at a temperature not exceeding 25 °C.

Keep out of the reach of children.

1. International nonproprietary name: no. Chemical name: Ferric (III) hydroxide saccharose complex.

2. Main synonyms: Venofer.

3. Pharmacotherapeutic group. Antianemic drugs. Iron supplements.

4. Main pharmacotherapeutic action and effects. Antianemic, replenishing iron deficiency. Increases the iron content in the body, which ensures the synthesis of heme (hemoglobin, myoglobin, cytochrome) and non-heme enzymes.

5. Summary of evidence of effectiveness. There are many publications on the effectiveness of iron (III) hydroxide sucrose complex in the treatment of iron deficiency anemia ( level of evidence strength A).

6. Brief results of pharmacoeconomic studies. No data.

7. Pharmacodynamics, pharmacokinetics, bioequivalence for analogs. The polynuclear iron(III) hydroxide centers are surrounded on the outside by many non-covalently bound sucrose molecules. As a result, a complex is formed, the molecular weight of which is approximately 43 kDa, as a result of which its excretion through the kidneys in unchanged form is impossible. This complex is stable and does not release iron ions under physiological conditions. The iron in this complex is bound to structures similar to natural ferritin.

After a single intravenous injection of a drug containing 100 mg of iron, the maximum concentration of iron, on average 538 mu mol, is achieved 10 minutes after injection. The volume of distribution of the central chamber almost completely corresponds to the volume of serum (about 3 l).

The half-life is about 6 hours. The volume of distribution at steady state is approximately 8 liters, indicating a low distribution of iron in body fluids. Due to the low stability of iron sucrose in comparison with transferrin, there is a competitive exchange of iron in favor of transferrin and as a result, about 31 mg of iron is transferred in 24 hours.

Iron excretion by the kidneys during the first 4 hours after injection is less than 5% of the total clearance. After 24 hours, the serum iron level returns to its original (pre-administration) value, and approximately 75% of sucrose leaves the vascular bed.

8. Indications. If you need to quickly replenish iron; in patients who cannot tolerate oral iron supplements; in the presence of active inflammatory bowel diseases, when oral iron supplements are ineffective.

9. Contraindications. Anemia is not due to iron deficiency; there are signs of iron overload (hemosiderosis, hemochromatosis) or a violation of the process of its utilization; there is hypersensitivity to the drug or its inactive components; I trimester of pregnancy.

10. Performance criteria. Reticulocyte crisis (2 - 10-fold increase in the number of reticulocytes on the 5th - 8th day of treatment compared to the initial value), in the 3rd week an increase in hemoglobin and the number of red blood cells.

11. Principles of selection, dose changes and withdrawal.

Before administering the first therapeutic dose, it is necessary to prescribe a test dose: 20 mg of iron for adults and children weighing more than 14 kg, and half the daily dose (1.5 mg iron/kg) for children weighing less than 14 kg over 15 minutes. . In the absence of adverse events, the remainder of the solution should be administered at the recommended rate. If during the observation period phenomena of intolerance occur, administration of the drug should be stopped immediately.

It is preferable to administer the drug as a drip infusion in order to reduce the risk of a pronounced decrease in blood pressure and the risk of the solution entering the perivenous space. Immediately before infusion, the drug must be diluted with 0.9% sodium chloride solution in a ratio of 1:20 (for example, 1 ml (20 mg of iron) in 20 ml of 0.9% sodium chloride solution). The resulting solution is administered at the following speed: 100 mg of iron - no less than 15 minutes; 200 mg of iron - within 30 minutes; 300 mg of iron - for 1.5 hours; 400 mg of iron - for 2.5 hours; 500 mg of iron - over 3.5 hours. The maximum tolerated single dose of 7 mg iron/kg body weight should be administered over a minimum of 3.5 hours, regardless of the total dose of the drug.

The drug can also be administered in the form of an undiluted solution intravenously slowly, at a rate (norm) of 1 ml of the drug (20 mg of iron) per minute (5 ml of the drug (100 mg of iron) is administered no faster than 5 minutes). The maximum volume of the drug should not exceed 10 ml of the drug (200 mg of iron) per injection.

The drug can be administered directly into the venous portion of the dialysis system, strictly following the rules described for intravenous injection.

The dose is calculated individually in accordance with the general iron deficiency in the body using the formula:

Total iron deficiency (mg) = body weight/body weight (kg) x (normal Hb level - patient's Hb) (g/l) x 0.24 + deposited iron (mg).

For patients weighing less than 35 kg: normal Hb level = 130 g/l, amount of deposited iron = 15 mg/kg body weight

For patients weighing more than 35 kg: normal Hb level = 150 g/l, amount of deposited iron = 500 mg

Coefficient 0.24 = 0.0034 x 0.07 x 1000 (iron content in Hb = 0.34%; blood volume = 7% of body weight; coefficient 1000 = conversion of “g” to “mg”).

Total volume of drug to be administered (in ml):

Total iron deficiency (mg)

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In cases where the total therapeutic dose exceeds the maximum permissible single dose, split administration of the drug is recommended.

If 1 to 2 weeks after the start of treatment with the drug there is no improvement in hemoglobin levels, it is necessary to reconsider the initial diagnosis.

Dose calculation for replenishing iron levels after blood loss or autologous blood donation:

The dose of the drug required to compensate for iron deficiency is calculated using the following formula:

If the amount of blood lost is known: intravenous administration of 200 mg of iron (equal to 10 ml of the drug) leads to the same increase in hemoglobin concentration as a transfusion of 1 unit of blood (equal to 400 ml with a hemoglobin concentration of 150 g / l).

Iron quantity, Quantity

which is needed = units x 200

replenish (mg) lost blood

Required volume Quantity

drug (ml) = units x 10.

lost blood

If hemoglobin levels decrease: use the previous formula, provided that iron depots do not need to be replenished.

Quantity │ │

iron, mass │ normal level │

which = body x 0.24 x │ level - hemoglobin│

required (kg) │patient hemoglobin │

replenish │ (g/l) │

For example: body weight 60 kg, hemoglobin deficiency = 10 g/l, => required amount of iron<->150 mg => required volume of drug = 7.5 ml

Maximum tolerated single dose:

For jet administration: 10 ml of the drug (200 mg of iron), duration of administration of at least 10 minutes.

For drip administration, depending on the indications, a single dose can reach 500 mg of iron. The maximum permissible single dose is 7 mg of iron per kg of body weight and is administered once a week, but it should not exceed 500 mg of iron. For patients donating 420 ml of blood weekly before surgery for subsequent autologous blood transfusion, it is recommended that 5 times intravenous administration of 200 mg of iron be administered weekly one month before surgery.

The drug is discontinued if the drug is ineffective and an allergic reaction to the drug occurs.

12. Overdose. Overdose can cause acute iron overload, which manifests itself as symptoms of hemosiderosis. In case of overdose, it is recommended to use symptomatic agents and, if necessary, iron-binding substances (chelates), for example IV deferoxamine. Treatment: in case of severe poisoning, desferoxamine is slowly administered intravenously: children - 15 mg/h, adults - 5 mg/(kg per hour) (up to 80 mg/(kg per day)); for mild poisoning - intramuscularly for children - 1 g every 4 - 6 hours, for adults - 50 mg/kg (up to 4 g/day).

13. Warnings and information for medical personnel. The drug is administered only intravenously: stream (slowly) or drip, as well as into the venous section of the dialysis system and is not intended for intramuscular administration. It is not permissible to administer the full dose, i.e. a dose that would completely compensate for the lack of iron in the patient’s body, in the form of a one-time infusion. Before opening, the ampoule must be inspected for possible sediment and damage. Precipitation may form if stored improperly; ampoules must be checked before injection. Only brown solution without sediment can be used.

Penetration of the drug into the perivenous space should be avoided, because penetration of the drug outside the vessel leads to tissue necrosis and brown discoloration of the skin. If this complication develops, to accelerate the removal of iron and prevent its further penetration into surrounding tissues, it is recommended to apply heparin-containing drugs to the injection site (apply the gel or ointment with light movements, without rubbing).

14. Features of use and restrictions in old age, with insufficiency of liver, kidney, etc.

Standard dosage: Adults and elderly patients: 5 - 10 ml of the drug (100 - 200 mg iron) 1 - 3 times a week depending on the hemoglobin level. There are only limited data on the use of the drug in children. If necessary, it is recommended to administer no more than 0.15 ml of the drug (3 mg of iron) per kg of body weight 1 - 3 times a week, depending on the hemoglobin level.

Use with caution in patients with bronchial asthma, eczema, polyvalent allergies, allergic reactions to other parenteral iron preparations due to the high risk of developing allergic reactions. Caution is also required when administering iron supplements to patients with liver failure, acute or chronic infectious diseases, and individuals with low serum iron-binding capacity and/or folic acid deficiency.

15. Side effects and complications. The following adverse events are currently known to have a temporary and possible causal relationship with the administration of the drug. All symptoms were observed very rarely (incidence of occurrence less than 0.01% and greater than or equal to 0.001%): dizziness, headache, loss of consciousness, paresthesia, palpitations, tachycardia, decreased blood pressure, collapsed states, feeling of heat, “flushes” of blood face, peripheral edema, bronchospasm, shortness of breath, diffuse abdominal pain, pain in the epigastric region, diarrhea, taste disturbance, nausea, vomiting, erythema, itching, rash, pigmentation disorder, increased sweating, arthralgia, back pain, joint swelling, myalgia, pain in the extremities, anaphylactic reactions, swelling of the face, swelling of the larynx, asthenia, chest pain, feeling of heaviness in the chest, weakness, pain and swelling at the injection site (especially with extravasal exposure of the drug), feeling of malaise, pallor, fever, chills.

16. Interaction with other drugs. The drug should not be prescribed simultaneously with dosage forms of iron for oral administration, as it helps to reduce the absorption of iron from the gastrointestinal tract. Treatment with oral iron supplements can begin no earlier than 5 days after the last injection.

17. Use of medicine as part of complex medicines. Not applicable.

18. Cautions and Patient Information. Keep medications away from children.

19. Additional requirements for the patient's informed consent. Explain the nature, purpose, duration, and information about possible adverse effects of treatment.

20. Release form, dosage. Venofer, ampoules (5 ml) containing 100 mg of iron. 5 ampoules are placed in a polyvinyl chloride blister pack, which, together with instructions for use, is placed in a cardboard box.

21. Storage features. In a place protected from light.