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

solution for intravenous administration

Each ampoule contains:

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

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

Dark brown colloidal solution.

The polynuclear centers of iron (III) hydroxide 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 - the physiological depot of iron. This complex is designed to create a controlled source of utilizable 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 mainly by the liver, spleen and bone marrow, and then used to synthesize hemoglobin, myoglobin and other iron-containing enzymes, or stored in the liver in the form of ferritin.

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

The half-life is about 6 hours. The volume of distribution in the equilibrium state is approximately 8 liters, which indicates a low distribution of iron in body fluids, due to the low stability of iron saccharate in comparison with transferrin, there is a competitive exchange of iron in favor of transferrin and, as a result, for 24 h transfers about 31 mg of iron.

The excretion of iron 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 (before 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 necessary, rapid replenishment of iron;
• in patients who do not tolerate oral iron preparations or do not comply with the treatment regimen;
• in the presence of active inflammatory bowel disease, when oral iron preparations 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 an increased sensitivity 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 those with low serum iron-binding capacity and / or folic acid deficiency Iron hydroxide sucrose complex should be administered with caution.

Also, caution is required when administering iron preparations to patients with liver failure, with acute or chronic infectious diseases, and in persons who have elevated serum ferritin levels due to the fact that parenteral iron can 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 showed no undesirable effect 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 adverse effects on embryonic/fetal development, parturition or postnatal development. However, an assessment of the risk/benefit ratio is required.

It is unlikely that unmetabolized iron saccharate will pass into breast milk. Thus, iron hydroxide sucrose complex does not pose a risk to breastfed infants.

Introduction: Iron hydroxide sucrose complex is administered only intravenously - slowly by 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 the introduction of the first therapeutic dose, it is necessary to prescribe a test dose. If intolerance occurs during the observation period, the administration of the drug should be stopped immediately. Before opening, the ampoule should be inspected for possible sediment and damage. Only brown solution without sediment can be used.

Drip Introduction: the drug Iron hydroxide sucrose complex is preferably administered 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 Iron hydroxide sucrose complex should be diluted with 0.9% sodium chloride solution in a ratio of 1:20 [for example, I ml (20 mg of iron) in 20 ml of 0.9% sodium chloride solution]. The resulting solution is injected at the following rate: 100 mg of iron - not less than 15 minutes; 200 mg of iron - within 30 minutes; 300 mg of iron - for 1.5 hours; 400 mg of iron - within 2.5 hours; 500 mg of iron - for 3.5 hours. The introduction of the maximum tolerated single dose of 7 mg of iron / kg of body weight should be made for at least 3.5 hours, regardless of the total dose of the drug.

Before the first drip injection of a therapeutic dose of Iron hydroxide sucrose complex, a test dose should be administered: 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 within 15 min. In the absence of adverse events, the remainder of the solution should be administered at the recommended rate.

Inkjet introduction: Iron preparation sucrose complex hydroxide can also be administered as an undiluted solution intravenously slowly, at a rate (norm) 1 ml Iron hydroxide sucrose complex (20 mg iron) in one minute (5 ml Iron hydroxide sucrose complex (100 mg iron) preparation minimum for 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 bolus injection of a therapeutic dose of Iron hydroxide sucrose complex, a test dose should be prescribed: 1 ml of Iron hydroxide sucrose complex (20 mg iron) in 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 for 1-2 minutes. In the absence of 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 advised to fix the arm in an extended position for a while.

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

Dose calculation: The dose is calculated individually according to the total iron deficiency in the body using the formula:

Total iron deficiency (mg) \u003d body weight (kg) x (normal level of H b - Hb of the patient) (g / l) x 0.24 * + deposited iron (mg).

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

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

* Factor 0.24 = 0.0034 x 0.07 x 1000 (Iron content in Hb = 0.34%; Blood volume = 7% of body weight; factor 1000 = convert "g" to "mg").

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

In the case when the total therapeutic dose exceeds the maximum allowable single dose, fractional 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 compensate for iron deficiency after blood loss or autologous blood donation:

The dose of 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 preparation Iron hydroxide sucrose complex) leads to the same increase in the concentration of Hb as a transfusion of 1 unit of blood (= 400 ml with an Hb concentration of 150 g/l).

Iron Needed to be Replaced (mg) = Blood Units Lost x 200 OR

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

number of lost blood units x 10

With a decreaseHb: use the previous formula, provided that the iron depot does not need to be replenished.

The amount of iron 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 in 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 the level of hemoglobin.

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 not more than 0.15 ml of Iron hydroxide sucrose complex (3 mg of iron) per kg of body weight 1-3 times a week, depending on the level of hemoglobin.

Maximum tolerated single dose:

Adults and elderly patients:

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

For drip administration: depending on the indications, a single dose can reach 500 mg of iron. The maximum allowable 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 commonly reported adverse drug reactions with iron hydroxide sucrose complex preparations were changes in taste sensations, 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 side of the immune system

Rare: anaphylactoid reactions.

From the side of the nervous system

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

From the side of the heart

Uncommon: tachycardia, palpitations. Not known: bradycardia.

From the side of the vessels

Uncommon: decrease in blood pressure. vascular collapse. Rare: increased blood pressure.

Respiratory, thoracic and mediastinal

Uncommon: bronchospasm, dyspnoea.

From the gastrointestinal tract

Uncommon: nausea, vomiting, abdominal pain, diarrhea.

From the side of the skin and subcutaneous tissues

Uncommon: pruritus, urticaria, rash, erythema

From the side of the musculoskeletal system and connective tissue

Infrequent: 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 hot, edema. Very rare: hyperhidrosis, back pain. Not known: chromaturia.

Overdose can cause acute iron overload, which is manifested by symptoms of hemosiderosis. In case of overdose, it is recommended to use symptomatic agents and, if necessary, iron-binding agents (chelates), for example, intravenously.

Iron hydroxide sucrose complex should not be administered simultaneously with oral iron dosage forms, as it helps to reduce the absorption of iron from the gastrointestinal tract. Treatment with oral iron preparations 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 agents 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 relevant laboratory data (for example, the results of determining serum ferritin or hemoglobin and hematocrit levels, the number of erythrocytes and their parameters - the average erythrocyte volume, the average content, hemoglobin in the erythrocyte or the average: concentration of hemoglobin in the erythrocyte).

Intravenous iron preparations can 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 the rapid administration of the drug, blood pressure may decrease). A higher incidence of adverse events (particularly a decrease in blood pressure), which can also be severe, is associated with an increase in dose. Thus, the time of administration of the drug given in the section "Methods of administration and doses" must be strictly observed, even if the patient does not receive the drug in the maximum tolerated single dose.

Studies conducted in patients with hypersensitivity reactions to iron dextran showed no complications during treatment with iron preparations of sucrose hydroxide complex.

Penetration of the drug into the perivenous space should be avoided, tk. the ingestion of the drug Iron hydroxide sucrose complex outside the vessel leads to tissue necrosis and brown staining of the skin. In the event of the development of this complication, in order to accelerate the excretion of iron and prevent its further penetration into the surrounding tissues, it is recommended that heparin-containing preparations be applied to the injection site (gel or ointment is applied with light movements, without rubbing).

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

It is unlikely that the drug Iron hydroxide sucrose complex can have an undesirable effect on the ability to drive a car and work with mechanisms. However, with the development of symptoms such as dizziness, confusion or fainting, patients should not drive vehicles or mechanisms until these symptoms disappear.

Solution for intravenous administration 20 mg/ml.

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

5 ampoules in a plastic tray.

1 plastic pallet together with instructions for use is placed in a cardboard box.

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

Keep out of the reach of children.

1. International non-proprietary name: no. Chemical name: iron (III) - hydroxide sucrose complex (Ferric (III) hydroxide sacharose complex).

2. Main synonyms: Venofer.

3. Pharmacotherapeutic group. Antianemic agents. Iron preparations.

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

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

6. Brief results of pharmacoeconomic studies. No data.

7. Pharmacodynamics, pharmacokinetics, bioequivalence for analogues. The polynuclear centers of iron (III) hydroxide 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 kD, 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 associated with structures similar to natural ferritin.

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

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 saccharate compared to 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.

The excretion of iron 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 (before administration) value, and approximately 75% of the sucrose leaves the vascular bed.

8. Indications. If necessary, rapid replenishment of iron; in patients who cannot tolerate oral iron preparations; in the presence of active inflammatory bowel disease, when oral iron preparations are ineffective.

9. Contraindications. 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 or its inactive components; I trimester of pregnancy.

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

11. Principles of selection, dose changes and withdrawal.

Before the introduction of 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 for 15 minutes . In the absence of adverse events, the remainder of the solution should be administered at the recommended rate. If intolerance occurs during the observation period, the 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 injected at the following rate: 100 mg of iron - not less than 15 minutes; 200 mg of iron - within 30 minutes; 300 mg of iron - for 1.5 hours; 400 mg of iron - within 2.5 hours; 500 mg of iron - for 3.5 hours. The introduction of the maximum tolerated single dose of 7 mg of iron / kg of body weight should be made for at least 3.5 hours, regardless of the total dose of the drug.

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

The dose is calculated individually according to the general deficiency of iron in the body according to the formula:

Total iron deficiency (mg) \u003d body weight / body weight (kg) x (normal level of Hb - Hb of the patient) (g / l) x 0.24 + deposited iron (mg).

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

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

Coefficient 0.24 \u003d 0.0034 x 0.07 x 1000 (iron content in Hb \u003d 0.34%; blood volume \u003d 7% of body weight; coefficient 1000 \u003d conversion "g" to "mg").

The total volume of the drug to be administered (in ml):

Total iron deficiency (mg)

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In the case when the total therapeutic dose exceeds the maximum allowable single dose, fractional administration of the drug is recommended.

If after 1-2 weeks after the start of treatment with the drug there is no improvement in hemoglobin values, 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).

The amount of iron, Amount

which is needed = units x 200

replenish (mg) of lost blood

Required volume Quantity

drug (ml) = units x 10.

lost blood

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

Quantity │ │

iron, mass │ normal level │

which \u003d body x 0.24 x │ level - hemoglobin │

necessary (kg) │ hemoglobin of the patient │

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), the duration of administration is at least 10 minutes.

For drip administration, depending on the indications, a single dose can reach 500 mg of iron. The maximum allowable 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. Patients who donate 420 ml of blood weekly before surgery for subsequent autologous blood transfusion are recommended to receive 5 intravenous injections of 200 mg of iron weekly a month before surgery.

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

12. Overdose. Overdose can cause acute iron overload, which is manifested by symptoms of hemosiderosis. In case of overdose, it is recommended to use symptomatic agents and, if necessary, iron-binding agents (chelates), such as IV deferoxamine. Treatment: in case of severe poisoning, desferoxamine is slowly injected intravenously: for children - 15 mg / h, for adults - 5 mg / (kg per hour) (up to 80 mg / (kg per day)); with mild poisoning - intramuscularly for children - 1 g every 4 to 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: jet (slowly) or drip, as well as into the venous area of ​​the dialysis system and is not intended for intramuscular injection. It is not permissible to administer a 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 single infusion. Before opening, the ampoule should be inspected for possible sediment and damage. Sedimentation is possible if stored incorrectly, it is necessary to check the ampoules before injection. Only brown solution without sediment can be used.

Penetration of the drug into the perivenous space should be avoided, tk. getting the drug outside the vessel leads to tissue necrosis and brown staining of the skin. In the event of the development of this complication, in order to accelerate the excretion of iron and prevent its further penetration into the surrounding tissues, it is recommended to apply heparin-containing preparations to the injection site (gel or ointment is applied with light movements, without rubbing).

14. Features of use and restrictions in the elderly, with insufficiency of the liver, kidneys, etc.

Standard dosage: Adults and elderly patients: 5 - 10 ml of the drug (100 - 200 mg of iron) 1 - 3 times a week, depending on the level of hemoglobin. 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 to 3 times a week, depending on the level of hemoglobin.

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 hepatic insufficiency, acute or chronic infectious diseases, and individuals with low serum iron-binding capacity and / or folic acid deficiency.

15. Side effects and complications. Currently, the following adverse events are known to have a temporal and possible causal relationship with the administration of the drug. All symptoms were observed very rarely (incidence less than 0.01% and greater than or equal to 0.001%): dizziness, headache, loss of consciousness, paresthesia, palpitations, tachycardia, lowering blood pressure, collaptoid states, feeling hot, flushing face, peripheral edema, bronchospasm, shortness of breath, diffuse abdominal pain, pain in the epigastric region, diarrhea, taste perversion, nausea, vomiting, erythema, itching, rash, pigmentation disorders, increased sweating, arthralgia, back pain, swelling of the joints, myalgia, pain in the extremities, anaphylactic reactions, swelling of the face, swelling of the larynx, asthenia, chest pain, a feeling of heaviness in the chest, weakness, pain and swelling at the injection site (especially with extravasal ingestion of the drug), feeling unwell, pallor, fever, chills.

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

17. The use of drugs in the composition of complex drugs. Not applicable.

18. Warnings and information for the patient. Keep medicines away from children.

19. Additional requirements for the informed consent of the patient. 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 blisters, which, together with instructions for use, are placed in a cardboard box.

21. Features of storage. In a place protected from light.