Likferr 100 (Iron (III) hydroxide dextran) 20mg/ml 5ml 5 vials

Description pharmaceutical form:

A colloidal solution from red-brown to brown.

Pharmacokinetics:

After a single on/in the introduction of the drug Likferr 100 containing 100 mg iron, iron Cmax (on average, 538 mol) is reached after 10 min after injection. T1/2 is 6 h. the VSS at steady state is approximately 8 l that indicates low iron distribution in liquid media of the organism.

Release of iron by the kidneys the first 4 h after injection is less than 5% of total clearance. After 24 h of serum iron content is returned to the original (before the introduction) value, and approximately 75% of the sucrose leaves the bloodstream.

Description pharmacological action:

Drug gland regulates metabolic processes. Is a colloidal solution, which consists of spheroidal iron-carbohydrate nanoparticles. In the nucleus (center) of each particle is iron (III) hydroxide. The nucleus is surrounded by a shell of sucrose, which stabilizes the iron (III)-hydroxide slowly releases the bioactive iron, and maintains the resulting particles in colloidal solution. The result is a complex molecular mass of approximately 43 kDa, resulting in its excretion via the kidneys in unchanged form is not possible. Iron (III) in this complex is associated with structures similar to the natural San.

The active ingredient of the drug is iron (III)-hydroxide sucrose complex — when ingested, dissociates in the reticuloendothelial system into iron and sucrose. Due to the lower stability of iron saharata compared to transferrin is observed in competitive exchange of iron to transferrin favor. As a result, 24 hours over about 31 mg of iron. Polycyclic ferric hydroxide (III) is partially preserved in the form of ferritin after complex formation with the protein ligand — apoferritin liver mitochondria. The rate of hemoglobin increases faster and with more certainty than after the therapy, drugs containing iron (II). The introduction of 100 mg of iron (III) leads to an increase of hemoglobin of 2-3% during pregnancy by 2%. The toxicity of the drug is very low. Therapeutic index equal to 30 (200/7).

Indications:

Iron deficiency States (including iron deficiency and acute post-hemorrhagic anemia) patients with the following conditions:

• the need for rapid replenishment of iron
• intolerance to oral iron
• diseases of the digestive tract that make it impossible oral iron supplementation..

Contraindications:

• hypersensitivity to the drug Likferr 100
• anemia not associated with iron deficiency
• signs of iron overload (hemosiderosis, hemochromatosis) or violation of the process of its utilization
• The first trimester of pregnancy (see “pregnancy and breastfeeding”).

With caution:

• bronchial asthma
• eczema
• polyvalent Allergy, allergic reactions to other parenteral iron preparations (due to high risk of developing allergic reactions — see section “Special instructions”)
• liver failure
• acute infectious diseases
• low iron binding capacity the ability of serum and/or folic acid deficiency
• diabetes mellitus (see “Special instructions”)
• children’s age (under 18) (due to the lack of data on safety and efficacy).

Application of pregnancy and breast-feeding:

The drug is contraindicated in the first trimester of pregnancy. In II and III trimester of pregnancy only if the expected benefit to the mother outweighs the potential risk to the fetus. Lactation the safety of the drug is not installed. It is recommended to stop breast-feeding (if necessary, use of the drug) or stop the drug.

Side effects:

CNS: dizziness, headache, loss of consciousness, paresthesia.

From the side of cardiovascular system: palpitations, tachycardia, decreased blood pressure, kollaptoidnoe state, feeling heat, tides blood to a person, peripheral edema.

The respiratory system: bronchospasm, shortness of breath.

From the digestive system: transient taste disturbances (especially metallic taste in the mouth), “spilled” abdominal pain, epigastric pain, diarrhea, dysgeusia, nausea, vomiting.

With the skin: erythema, pruritus, rash, pigmentation disorders, increased sweating.

From the musculoskeletal: arthralgia, back pain, swelling of joints, myalgia, pain in extremities.

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

Other: asthenia, chest pain, back, a feeling of heaviness in the chest, weakness, feeling of malaise, pallor, fever, chills.

Local reactions: pain and swelling at the injection site (especially when ekstrawazalnoe contact of the drug), phlebitis, burning sensation, hematoma.

If any of these side effects worsen or develop any other side effects, you should inform the doctor.

Drug interactions:

Unacceptable simultaneous use of the drug Likferr 100 with medicinal forms of iron intake, because it decreases iron absorption from the gastrointestinal tract. Treatment with oral iron preparations can begin no earlier than 5 days after the last injection.

Likferr 100 can be mixed in the same syringe only with 0.9% sodium chloride solution. No other solution for I/V administration and therapeutic products add not allowed because there is a risk of precipitation and/or other pharmaceutical interaction. Compatibility with containers of other materials than glass, PE and PVC, has not been studied.

If the patient takes other medications, you should consult with your doctor.

Method of application and dose:

Introduction

In/in (slow struino or drip) and in the venous phase of dialysis system. The drug is not intended for the/m introduction. Unacceptable simultaneous introduction of full (cumulative) therapeutic doses of the drug.

Before the introduction of the first therapeutic dose, it is necessary to assign a test dose. If during the observation period appeared the phenomenon of intolerance, the drug should be discontinued immediately. Before opening, ampoules should examine her for possible sediment and damage. You can use only a brown solution without sediment.

Drip

Likferr 100 preferable to introduce in the course of drip infusion in order to reduce the risk of pronounced blood pressure reduction and the risk of contact with okolovenoznoe space. Just before infusion Likferr 100 should be diluted with 0.9% sodium chloride solution in ratio of 1:20, e.g. 1 ml (20 mg iron) in 20 ml of 0.9% solution of sodium chloride. The resulting solution is introduced with the following speed: 100 mg of iron is not less than 15 min 200 mg over 30 min 300 mg for 1.5 h, 400 mg over 2.5 h 500 mg for 3.5 h. The introduction of the maximum tolerated dose, estimated at 7 mg iron/kg should be made for at least 3.5 h, regardless of the total dose.

Before the first drip by introduction of a therapeutic dose of the drug Likferr 100 you must enter test dose: 1 ml Likferr 100 (20 mg iron) in adults and children weighing more than 14 kg and half the daily dose (1.5 mg iron/kg) to children with body weight less than 14 kg, for 15 min. in the absence of undesirable phenomena, the remaining solution should be administered with the recommended speed.

Bolus

The drug Likferr 100 you can also enter in the form of undiluted solution in/in slowly, with a speed of 1 ml Likferr 100 (20 mg iron) per minute, for example 5 ml Likferr 100 (100 mg iron) injected within 5 min, the Maximum volume should not exceed 10 ml Likferr 100 (200 mg iron) per injection.

After injection, the patient is recommended some time to fix arm in extended position.

Before the first jet by the introduction of the therapeutic dose should be administered Likferr 100 test dose: 1 ml Likferr 100 (20 mg iron) in adults and children weighing more than 14 kg and half the daily dose (1.5 mg iron/kg) to children with body weight less than 14 kg over 1-2 min If no adverse effects during subsequent 15 min of observation the remainder of the solution should be administered with the recommended speed. After injection, the patient is recommended to stabilize the hand in a stretched position.

Introduction to dialysis system

Likferr 100 possible to enter directly into the venous phase of dialysis system, strictly observing the rules outlined for intravenous injection.

The calculation of the dose

Before the introduction it is necessary to individually calculate the total body iron deficiency according to the following formula:

Total iron deficit (mg) = body weight (kg) ? (Нb OK — Нb patient (g/l) ? 0,24 + deposited iron (mg)

For patients with body weight less than 35 kg:

– the number of the deposited iron = 15 mg/kg,

– the normal rate Нb = 130 g/l.

For patients weighing over 35 kg:

– the number of the deposited iron = 500 mg,

– the normal rate Нb = 150 g/l.

The coefficient 0,24 = 0,0034 ? 0,07 ? 1000 (iron content of hemoglobin = 0.34 percent blood volume = 7% of body weight factor 1000 = conversion from the grams in miligram).

You then need to calculate the cumulative (course) dose of the drug Likferr 100 that you need to enter to fill the deficit of iron in the body, according to the following formula:

Total volume (ml) = Total iron deficit (mg)/ 20 mg/ml

Approximate values of total iron deficiency and the total amount of the preparation for the introduction of the course of therapy are shown in table:

Table

The total amount of the drug for the treatment of Likferr 100

The frequency of administration is determined by a physician, but not more often than every other day.

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

Children: there are limited data on the use of drugs in children. If necessary, it is recommended to enter a maximum of 0.15 ml Likferr 100 (3 mg iron)/kg 1-3 times per week depending on the indicator Нb.

The maximum tolerated single dose for adults, including elderly (>65 years) patients

For jet injection: 10 ml Likferr 100 (200 mg iron), the duration of administration — not less than 10 min.

For intravenous injection: depending on indications, a single dose can be 500 mg of iron. The maximum allowable single dose of 7 mg iron/kg, and is injected once a week, but not more than 500 mg of iron.

Usually, higher doses are associated with a higher frequency of adverse events.

In the case when the total therapeutic dose exceeds the maximum allowed single dose, it is recommended that the fractional drug.

If after 1-2 weeks after the start of drug treatment Likferr 100 is no improvement of hematological parameters, it is necessary to reconsider the initial diagnosis.

The calculation of the dose to compensate the iron content after the blood loss or even autologous blood

Dose Likferr 100 needed to compensate for the iron deficiency, is calculated by the following formula:

If the amount of blood lost is known: in/with the introduction of 200 mg iron (10 ml Likferr 100) leads to the same increase in the concentration Нb as the transfusion of 1 unit of blood (400 ml with the concentration of Нb 150 g/l).

The amount of iron that needs to be filled up, mg = number of units blood lost x 200 or the necessary amount of the drug Likferr 100, ml = number of blood units lost x 10.

While reducing the content of Нb: use the previous formula, provided that the depot iron Supplement is required.

The amount of iron that need to be filled in mg = body weight, kg x 0.24 x (normal rate Hb — patient Hb), g/l,

For example: weight 60 kg, Hb deficit = 10 g/l the necessary amount of iron = 150 ppm, the necessary amount of the drug Likferr 100 = 7.5 ml.

Treatment of patients with chronic renal disease undergoing hemodialysis and receiving erythropoietin treatment additional

The drug is administered strictly in a/V. the injection Itself should be performed as slowly as possible, the duration of injection increases with increasing dose. The procedure is not particularly difficult for hemodialysis patients, because they usually contain a suitable intravenous access. The drug is administered in 0.9% sodium chloride solution for at least 15 min during the last 2 hours of each dialysis session.

Absolute iron deficiency (phase of correction of anemia)

30-50 mg of iron/session dialysis

or

– 1000 mg of iron within 6-10 weeks.

Phase of maintenance therapy

Are assigned to different doses, in different modes:

– 10-25 mg of iron/session dialysis

or

– 100 mg of iron/ 1 time per month (depending on the ferritin concentration in serum).

Phase correction of hemoglobin

– 150 mg of iron to increase the concentration to 10 g/L.

Overdose:

Symptoms: decrease in blood pressure (signs of collapse seen within 30 min), symptoms of hemosiderosis.

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

Special instructions:

Should strictly observe the speed of the drug Likferr 100 (with the rapid introduction of the drug may drop BP). A higher incidence of undesirable side reactions (especially lower blood pressure), including and heavy, associated with increasing doses. Thus, the time of administration of the drug contained in the section “Method of application and dosage” should be strictly adhered to, even if the patient receives the drug at the maximum tolerated dose.

During the period of drug administration Likferr 100 need to monitor hemodynamic parameters.

Likferr 100 should be administered only to patients in whom the diagnosis of anaemia is confirmed by corresponding laboratory data (e.g. the results of determination of ferritin in serum or indicators of hemoglobin and hematocrit, number of erythrocytes and their parameters — average corpuscular volume or mean hemoglobin in the erythrocyte).

Intravenous iron preparations can cause allergic or anaphylactoid reactions that can be potentially life-threatening. Patients with asthma, eczema, atopic diseases, polyvalent Allergy, allergic reactions to other iron preparations, and patients with low iron binding capacity the ability of serum/or insufficiency of folic acid have an increased risk of allergic or anaphylactoid reactions (see section “Contraindications”, subsection “With caution”).

Studies conducted in patients who have hypersensitivity reactions to iron dextran showed no complications on the background of drug treatment.

Avoid penetration of the drug into okolovenoznoe space, since getting Likferr 100 beyond the vessel leading to tissue necrosis and brown staining of the skin. In the case of the development of this complication is recommended (if the needle is in the vessel) to introduce a small amount of 0.9% sodium chloride solution. To accelerate chelate iron and prevent its further penetration into surrounding tissue is recommended the application of the injection site geparinoterapii preparations (gel or ointment is applied lightly, not rubbing).

Unacceptable the introduction of the drug in the presence of sediment.

In 1 ml product contains Likferr 100 from 260 to 340 mg of sucrose. These data should be considered in patients with diabetes. In drip administered drug, depending on the indications, the maximum tolerated single dose can be 500 mg of iron, which corresponds to the introduction of 8.5 g of sucrose. In terms of the amount of carbohydrates in HYE (1 bread unit = 12 g of carbohydrates), it corresponds to 0.7 HEH.

During therapy with stimulants of erythropoiesis and iron metabolism is controlled by such factors as the concentration of serum ferritin and transferrin saturation with iron (scientific-technical journal+). Determining the number of hypochromic red blood cells and hemoglobin concentration in reticulocytes helps to make a decision about the necessity of appointment of iron preparations intravenously, when a scientific-technical journal + hyperferritinemia and low. The risk of iron overload kompensiruet blood loss during the procedures associated with dialysis (lost 1-3 g of iron per year). Should regularly monitor the concentration of ferritin in serum. The serum ferritin concentration above 500 µg/l (normal C-reactive protein counts), continuing for a long period of time can indicate the iatrogenic iron overload. In such cases the preparations of iron should be lifted (therapy with stimulants of erythropoiesis must continue). Due to the fact that iron stimulates the growth of most microorganisms, iron preparations should be discontinued in the development of acute bacterial infections. Also therapy with intravenous iron preparations should be used with caution in patients with permanent dialysis catheters.

Effects on ability to drive a vehicle or work with potentially dangerous machinery. We recommend caution when driving or operating potentially dangerous machinery.