Lycferr100,20 mg/ml 5 ml 5 pcs

Liqueferr100 is an anti-anemic.

Pharmacodynamics

The preparation of iron, regulates metabolic processes. It is a colloidal solution, which consists of spheroidal iron-carbohydrate nanoparticles. The core (center) of each particle contains iron (III) hydroxide. The core is surrounded by a sucrose shell, which stabilizes the iron (III) hydroxide, slowly releases the bioactive iron and keeps the resulting particles in colloidal solution. As a result, a complex is formed with a molecular weight of approximately 43 kDa, so that it cannot be excreted unchanged through the kidneys. Iron (III) in this complex is bound to structures similar to those of natural ferritin.

The active substance of the preparation – iron (III) hydroxide sucrose complex – dissociates into iron and sucrose in the reticuloendothelial system when entering the body. Due to the lower stability of iron sucrose compared to transferrin, there is a competitive exchange of iron in favor of transferrin. As a result, about 31 mg of iron is transferred in 24 h. Polycyclic iron (III) hydroxide is partially conserved as ferritin after complexation with the protein ligand, hepatic mitochondrial apoferritin. The hemoglobin index increases faster and with greater reliability than after therapy with iron (II)-containing drugs. Administration of 100 mg of iron (III) leads to an increase in hemoglobin by 2-3%; during pregnancy, 2%. The toxicity of the drug is very low. The therapeutic index is 30 (200/7).

Pharmacokinetics

After a single IV administration of Liquiferr100^® containing 100 mg of iron, the C_max of iron (average – 538 μmol) is reached 10 min after injection. T_1/2 is 6 h. V_ss is approximately 8 liters, indicating a low distribution of iron in the body fluids.

The renal excretion of iron for the first 4 h after injection is less than 5% of total clearance. After 24 h, serum iron content returns to the original (pre-injection) value and approximately 75% of sucrose leaves the vascular stream.

Indications

Anemia

Iron deficiency (including iron deficiency and acute posthemorrhagic anemia) in patients with the following conditions:

• need for rapid iron replenishment;
• intolerance of oral iron preparations;
• the presence of gastrointestinal diseases that make it impossible to take oral iron preparations.

Composition

Active substance:

Iron (III) hydroxide sucrose complex (in terms of iron (III)20 mg;

Auxiliary substances:

Sodium hydroxide – to pH 11;

water for injection – to 1 ml

How to take, the dosage

Intravenously (slow trickle or drip) and into the venous area of the dialysis system. The drug is not intended for intravenous administration. The full (cumulative) therapeutic dose of the drug must not be administered at one time.

Before the first therapeutic dose is administered, a test dose should be administered. If intolerance occurs during the observation period, the drug administration should be stopped immediately. Before opening the ampoule it should be inspected for possible sediment and damage. Only brown solution without residue may be used.

Drip administration

Liquiferr100^® is preferably administered by drip infusion in order to reduce the risk of marked BP decrease and the danger of solution entering the circulatory space. Immediately prior to infusion, Liquiferr100^® should be diluted with 0.9% sodium chloride solution at 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 rate: 100 mg of iron in at least 15 min; 200 mg within 30 min; 300 mg within 1.5 h; 400 mg within 2.5 h; 500 mg within 3.5 h. The maximum tolerated single dose of 7 mg of iron/kg should be administered for at least 3.5 h, regardless of the total dose of the drug.

Before the first drip administration of the therapeutic dose of Liquiferr100^®, a test dose should be administered: 1 ml of Likferr100^® (20 mg of iron) in adults and children with a body weight greater than 14 kg and half the daily dose (1.5 mg of iron/kg) in children with a body weight less than 14 kg for 15 min. In the absence of adverse events, the remainder of the solution should be administered at the recommended rate.

Stroke administration

Likferr100^® can also be administered as an undiluted solution slowly by IV at a rate of 1 ml of Liquferr100

sup>® (20 mg of iron) per minute – e.g. 5 ml of Liquiferr100^{® (100 mg of iron) administered within 5 minutes. The maximum drug volume should not exceed 10 ml of Liquferr100® (200 mg of iron) in one injection.}

After the injection, the patient is advised to fix the arm in an extended position for a moment.

Previously, a test dose should be given before the first administration of the therapeutic dose of Liquiferr100^®: 1 ml of Likferr100^® (20 mg of iron) in adults and children with a body weight greater than 14 kg and half the daily dose (1.5 mg of iron/kg) in children with a body weight less than 14 kg for 1-2 min. In the absence of adverse events during the next 15 min of observation, the remainder of the solution should be injected at the recommended rate. After injection, the patient is advised to fix the arm in an extended position.

Injection into the dialysis system

Liquiferr100^® can be injected directly into the venous area of the dialysis system, following the strict guidelines described for intravenous injection.

Dose calculation

Before administration, the total iron deficiency in the body must be calculated individually using the following formula:

Total iron deficiency (mg) = body weight (kg) × (normal Hb – patient Hb (g/l) × 0.24 + deposited iron (mg).

For patients with a body weight less than 35 kg:

• the amount of deposited iron = 15 mg/kg;
• normal Hb = 130 g/l.

For patients weighing more than 35 kg:

• Quantity of iron on deposit = 500 mg;
• normal Hb = 150 g/l.

The ratio 0.24 = 0.0034 × 0.07 × 1000 (hemoglobin iron content = 0.34%; blood volume = 7% of body weight; ratio 1000 = conversion from grams to milligrams).

Then the cumulative (course) dose of Likferr100^® to be administered to compensate for iron deficiency in the body should be calculated using the following formula:

Total drug volume (ml) = Total iron deficiency (mg)/ 20 mg/mL.

Adults, including elderly (over 65 years) patients: 5-10 ml of Likferr100^® (100-200 mg of iron) 1-3 times a week.

Children: There are only limited data on the use of the drug in children. If necessary, it is recommended to administer 0.15 ml or less of Likferr100^® (3 mg of iron)/kg 1-3 times weekly depending on the Hb values.

The maximum tolerated single dose for adults including elderly (over 65) patients

For jetting: 10 ml of Likferr100^® (200 mg of iron) and duration of administration is at least 10 minutes.

For drip administration: Depending on the indication, a single dose can be up to 500 mg of iron. The maximum permissible single dose is 7 mg of iron/kg and is administered once a week, but not more than 500 mg of iron.

Higher doses are generally associated with a higher incidence of adverse events.

If the total therapeutic dose is greater than the maximum tolerated single dose, fractional administration of the drug is recommended.

If there is no improvement in hematologic parameters 1-2 weeks after initiation of treatment with Likferr100^®, the initial diagnosis must be reconsidered.

Dose calculation for iron replacement after blood loss or autologous blood donation

The dose of Liquiferr100^® to compensate for iron deficiency is calculated using the formula below.

If the amount of blood lost is known: an intravenous infusion of 200 mg of iron (10 ml of Liquiferr100^®) produces the same increase in Hb concentration as a transfusion of 1 unit of blood (400 ml with a Hb concentration of 150 g/L).

The amount of iron to be replenished, mg = number of units of blood lost × 200 or the required volume of Liquiferr100^®, ml = number of units of blood lost × 10.

If the Hb count is decreased: use the previous formula provided the iron depot does not need to be replenished.

The amount of iron to be replenished, mg = body weight, kg × 0.24 × (normal Hb – patient Hb), g/l.

For example: body weight 60 kg, Hb deficiency = 10 g/l – amount of iron needed = 150 mg, needed amount of LIQUERR100^® = 7.5 ml.

Patients with chronic renal disease who are on hemodialysis and are receiving additional erythropoietin treatment

The drug is administered strictly by IV. The injection itself should be given as slowly as possible, with the duration increasing as the dose increases. The procedure is not particularly difficult for hemodialysis patients as they usually have suitable IV access. The drug is administered in 0.9% sodium chloride solution for at least 15 minutes during the last 2 hours of the hemodialysis session.

Absolute iron deficiency (anemia correction phase)

• 30-50 mg of iron/ dialysis session

or

• 1000 mg of iron for 6-10 weeks.

The maintenance therapy phase

Different doses are prescribed, in different regimens:

• 10-25 mg of iron/ dialysis session

or

• 100 mg of iron/ once a month (depending on serum ferritin concentration).

Hemoglobin correction phase

• 150 mg of iron to increase concentration by 10 g/l.

Interaction

The concomitant administration of Liquorr100^® with oral iron dosage forms is unacceptable because iron absorption from the gastrointestinal tract is reduced. Treatment with oral iron preparations can be started no earlier than 5 days after the last injection.

Liquefère100^® can only be mixed in the same syringe with 0.9% sodium chloride solution. No other I.V. solutions and therapeutic agents should be added since there is a risk of precipitation and/or other pharmaceutical interactions. Compatibility with containers made of materials other than glass, PE and PVC has not been studied.

If the patient is taking other medications, a physician should be consulted.

Special Instructions

The speed of administration of Liquiferr100^® should be strictly observed (BP may decrease if the drug is administered rapidly). A higher incidence of undesirable adverse reactions (especially – BP decrease), including severe ones, is associated with the dose increase. Therefore, the dosing times listed in the Administration and Doses section should be strictly adhered to, even if the patient is not receiving the drug in the maximum tolerated single dose.

Likferr100^® hemodynamic parameters must be monitored during administration.

Likferr100^® should be used only in patients whose diagnosis of anemia has been confirmed by appropriate laboratory data (e.g., serum ferritin or hemoglobin and hematocrit values, erythrocyte count and its parameters – mean erythrocyte volume or mean erythrocyte hemoglobin content).

Intravenous iron preparations can cause allergic or anaphylactoid reactions, which can be potentially life-threatening. Patients with bronchial asthma, eczema, atopic diseases, polyvalent allergies, allergic reactions to other iron preparations, and patients with low serum iron-binding capacity and/or folic acid deficiency have an increased risk of allergic or anaphylactoid reactions (see Contraindications, Caution).

Studies conducted in patients with hypersensitivity reactions to iron dextran have shown no complications with treatment with the drug.

Penetration of the drug into the periniferous space should be avoided because exposure of Liquiferr100^® outside of the vessel leads to tissue necrosis and brown staining of the skin. If this complication develops, it is recommended (if the needle is still in the vessel) to inject a small amount of 0.9% sodium chloride solution. To accelerate the elimination of iron and prevent its further penetration into the surrounding tissues it is recommended to apply heparin-containing preparations to the injection site (the gel or ointment is applied with light movements, without rubbing).

The drug should not be injected in the presence of sediment.

1 ml of Liquiferr100^® contains 260 to 340 mg of sucrose. This data should be considered in patients with diabetes mellitus. When administering the drug by drip, depending on the indications, the maximum tolerated single dose can be up to 500 mg of iron, which corresponds to administration of 8.5 g of sucrose. If this quantity of carbohydrate is converted into XU (1 XU = 12 g of carbohydrate), it corresponds to 0.7 XU.

During therapy with erythropoiesis stimulants, iron metabolism is monitored using indicators such as serum ferritin concentration and transferrin iron saturation (TTZ). Determination of the number of hypochromic erythrocytes and the hemoglobin concentration of the reticulocytes helps to decide whether IV iron preparations are needed when there is hyperferritinemia and low NTF. The risk of iron overload is compensated by blood loss during dialysis procedures (1-3 g of iron per year is lost). Serum ferritin concentrations should be monitored regularly. Serum ferritin concentrations above 500 µg/L (with normal C-reactive protein) that persist for a long time may indicate iatrogenic iron overload. In such cases, iron preparations should be discontinued (therapy with erythropoiesis stimulants should be continued). Due to the fact that iron stimulates the growth of most microorganisms, iron preparations should be withdrawn if acute bacterial infections develop. Also, IV iron therapy should be used with caution in patients with permanent dialysis catheters.

Impact on the ability to drive vehicles or operate potentially dangerous mechanisms. Caution is advised when driving a vehicle or operating potentially dangerous machinery.

Contraindications

• high sensitivity to components of Likferr100^®;
• anemia not related to iron deficiency;
• and signs of iron overload (hemosiderosis, hemochromatosis or impaired iron utilization;
• I trimester of pregnancy (see
• Pregnancy and pregnancy

.

• the presence of signs of iron overload (hemosiderosis, hemochromatosis) or impaired iron utilization;
• The first trimester of pregnancy (see “Use in pregnancy and lactation”). “

With caution: bronchial asthma; eczema; polyvalent allergies; allergic reactions to other parenteral iron preparations (due to the high risk of allergic reactions – see “Special Precautions. “

Particular indications); hepatic insufficiency; acute infectious diseases; low serum iron-binding capacity and/or folic acid deficiency; diabetes mellitus (see “Particular indications”); age under 18 years (due to insufficient safety and efficacy data).

Side effects

CNS disorders: dizziness, headache, loss of consciousness, paresthesias.

System adverse reactions: palpitations, tachycardia, decreased BP, collaptoid states, fever, flushes to the face, peripheral edema.

Respiratory system: bronchospasm, dyspnea.

Digestive system disorders: transient taste disorders (especially metallic taste in the mouth), pervasive abdominal pain, epigastric pain, diarrhea, perversion of taste, nausea, vomiting.

Skin disorders: erythema, itching, rash, impaired pigmentation, increased sweating.

Musculoskeletal system: arthralgia, back pain, joint swelling, myalgia, pain in the extremities.

Allergic reactions: anaphylactoid reactions, facial edema, laryngeal edema.

Others: asthenia, pain in the chest, back, feeling of heaviness in the chest, weakness, feeling of malaise, pallor, increased body temperature, chills.

Local reactions: pain and swelling at the injection site (especially if extravasal ingestion of the drug), phlebitis, burning sensation, hematoma.

Overdose

Symptoms: BP decrease (signs of collapse appear within 30 minutes), symptoms of hemosiderosis.

Treatment: symptomatic, if necessary – drugs that bind iron (chelators), such as deferoxamine.

Pregnancy use

The drug is contraindicated in the first trimester of pregnancy. In II and III trimesters of pregnancy the drug is used only if the estimated benefit to the mother exceeds the potential risk to the fetus.

The safety of the drug during lactation has not been established. It is recommended to stop breastfeeding (if the drug should be used) or to discontinue the drug.