Ликферр100®

General characteristics. Structure:

1 ml of drug contains in quality of active agent of iron [III] hydroxide a saccharose complex in terms of iron [III] – 20 mg;
excipients: sodium hydroxide, water for injections.

Description: colloidal solution from red-brown till brown color.

Pharmacological properties:

Pharmacodynamics. Iron preparation, regulates metabolic processes. Represents colloidal solution which consists of spheroidal iron-carbohydrate nanoparticles. In a kernel (center) of each particle there is an iron [III] hydroxide. The kernel is surrounded with a cover from sucrose which stabilizes iron [III] hydroxide, slowly releases bioactive iron and keeps the received particles in colloidal solution. The complex which molecular mass makes about 43 kd owing to what its removal through kidneys in not changed look is impossible is as a result formed. Iron [III] in this complex is connected with the structures similar to natural ferritin. Active agent of drug - gland [III] hydroxide dissociates a saccharose complex at hit in an organism in reticuloendothelial system on iron and sucrose. Thanks to lower stability of iron of saccharate in comparison with transferrin, competitive exchange of iron in favor of transferrin is observed. As a result for 24 h about 31 mg of iron are transferred. Polycyclic ferrous hydroxide [III] partially remains in the form of ferritin after a complex formation with a protein ligand - apoferritiny liver mitochondrions. The indicator of hemoglobin raises quicker and with bigger reliability, than after therapy by the medicines containing iron [II]. Introduction of 100 mg of iron [III] leads to increase in hemoglobin by 2-3%; during pregnancy - for 2%. Toxicity of drug very low. The therapeutic index is equal to 30 (200/7).

Pharmacokinetics. After single intravenous administration of the drug Likferr100 containing 100 mg of iron, the maximum concentration of iron (on average 538 µmol) it is reached 10 minutes later after an injection. An elimination half-life - 6 hours. Distribution volume in an equilibrium state makes about 8 l that indicates low distribution of iron in fluid mediums of an organism.

Release of iron kidneys after an injection makes the first 4 hours less than 5% of the general clearance. 24 hours later the content of iron of serum is returned to initial (before introduction) to value, and, about, 75% of sucrose are left by a vascular bed.

Indications to use:

- Iron deficiency states (including iron deficiency and acute posthemorrhagic anemia) at patients in need of bystry completion of iron;
- at patients who do not transfer peroral iron preparations;
- existence of diseases of the digestive tract (DT) at which peroral iron preparations cannot be used.

Route of administration and doses:

Likferr100 it is entered only intravenously

slowly struyno or kapelno, and also to the venous site of dialysis system it is also not intended for intramuscular introduction. Unacceptably single-step introduction of a full (cumulative) therapeutic dose of drug.

Before introduction of the first therapeutic dose, it is necessary to appoint a test dose. If during the period of observation there were intolerance phenomena, administration of drug should be stopped immediately. Before opening of an ampoule it is necessary to examine on existence of a possible deposit and damages. It is possible to use only brown solution without deposit.

Drop introduction

Likferr100 it is more preferable to enter during drop infusion to reduce risk of the expressed lowering of arterial pressure (ABP) and danger of hit of solution in perivenous space. Just before infusion of Likferr100 it is necessary to part 0,9% with chloride sodium solution in the ratio 1:20 [for example, 1 ml (20 mg of iron) in 20 ml of 0,9% of solution of sodium of chloride]. The received solution is entered with following skorostyyu:100 to iron mg - not less than in 15 minutes; 200 mg of iron - within 30 minutes; 300 mg of iron - within 1,5 hours; 400 mg of iron - within 2,5 hours; 500 mg of iron - within 3,5 hours. Introduction of the most tolerable single dose making 7 mg of iron/kg of body weight should be made within at least 3,5 hours, irrespective of the general dose of drug.

Before the first drop introduction of a therapeutic dose of the drug Likferr100, it is necessary to enter a test dose: 1 ml of the drug Likferr100 (20 mg of iron) to adults and children with body weight more than 14 kg, and a half of a day dose (1,5 mg of iron/kg) to the children having body weight less than 14 kg within 15 minutes. In the absence of the undesirable phenomena, the rest of solution should be entered with the recommended speed.

Jet introduction

The drug Likferr100 can also be administered in the form of not divorced solution intravenously slowly, with a speed of 1 ml of drug of Likferr100 (20 mg of iron) a minute (for example, 5 ml of the drug Likferr100 (100 mg of iron) are entered within         5 minutes). The maximum volume of drug should not exceed 10 ml of the drug Likferr100 (200 mg of iron) for one injection.

After an injection the patient is recommended to record for some time a hand in the extended situation.

Before the first jet introduction of a therapeutic dose of the drug Likferr100, it is necessary to enter a test dose: 1 ml of the drug Likferr100 (20 mg of iron) to adults and children with body weight more than 14 kg, and a half of a day dose (1,5 mg of iron/kg) to the children having body weight less than 14 kg within 1-2 minutes. In the absence of the undesirable phenomena within the next 15 minutes of observation, the rest of solution should be entered with the recommended speed. After an injection the patient is recommended to record a hand in the extended situation.

Introduction to dialysis system

Likferr100 it is possible to enter directly into the venous site of dialysis system, strictly following the rules described for an intravenous injection.

Calculation of a dose

Before introduction it is necessary to calculate individually the general deficit of iron in an organism by the following formula:

The general deficit of iron (mg) = the body weight (kg) x (Hb is normal
Hb of the patient (g/l)) x 0,24 + the deposited iron (mg)

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

For patients with body weight more than 35 kg:
amount of the deposited iron = 500 mg,
normal indicator of Hb = 150 g/l.
Coefficient 0,24 = 0,0034 x 0,07 x 1000 (content of iron in hemoglobin = 0,34%; blood volume = 7% of body weight; coefficient of 1000 = transfer from "" in "mg").
 
Then it is necessary to calculate a cumulative (course) dose of the drug Likferr100 which will need to be entered for completion of deficit of iron in an organism on the following formula:

The total amount of drug (in ml) = the General deficit of iron (mg) / 20 mg/ml

Approximate values of the general deficit of iron and total amount of drug for introduction on a course of therapy are given in the table:

Table.

The total amount of the drug Likferr100 for treatment
The body weight (kg) the Cumulative (course) therapeutic dose of the drug Likferr100 for introduction:
                 Hb of 60 g/l                  Hb of 75 g/l                Hb of 90 g/l            Hb of 105 g/l
                  mg of Fe   of ml               of mg of Fe  of ml                of mg of Fe   of ml           of mg of Fe  of ml
              5 160                         8 140                       7 120                  6 100       5
             10 320                       16 280                     14 240                12 220       11
             15 480                       24 420                     21 380               19 320      16
             20 640                       32 560                     28 500               25 420      21
             25 800                       40 700                     35 620                31 520      26
             30 960                      48 840                     42 740                37 640      32
            35 1260                      63 1140                   57 1000                50 880      44
            40 1360                      68 1220                   61 1080              54 940      47
            45 1480                      74 1320                   66 1140              57 980      49
            50 1580                      79 1400                   70 1220               61 1040    52
            55 1680                      84 1500                   75 1300              65 1100    55
            60 1800                      90 1580                   79 1360               68 1140    57
            65 1900                      95 1680                   84 1440               72 1200    60
              70 2020 101                    1760 88                    1500 75                 1260 63
              75 2120 106                    1860 93                    1580 79               1320 66
               80 2220 111                    1940 97                    1660 83               1360 68
              85 2340 117                   2040 102                  1720 86               1420 71
              90 2440 122                   2120 106                  1800 90                1480 74

Frequency rate of introduction is defined by the doctor, but not more often than every other day.

Adult, including elderly (65 years are more senior) patients: 5-10 ml of Likferr100 ( 100 - 200 mg of iron) 1-3 times a week.

Children: there are only limited data on use of drug for children. It is in case of need recommended to enter no more than 0,15 ml of the drug Likferr100   (3 mg of iron) on body weight kg 1-3 times a week depending on Hb indicator.

The most tolerable single dose (adult, including elderly (65 years) patients are more senior):

For jet introduction: 10 ml of the drug Likferr100 (200 mg of iron), duration of introduction are not less than 10 minutes.

For drop introduction: depending on indications the single dose can reach   500 mg of iron. The most admissible single dose makes 7 mg of iron on kg of body weight and is entered once a week, but it should not exceed 500 mg of iron.

Kak the rule, high doses are associated with higher frequency of the undesirable phenomena.

In case the general therapeutic dose exceeds the maximum admissible single dose, fractional administration of drug is recommended.

If 1-2 weeks later after an initiation of treatment improvement of hematologic indicators does not happen the drug Likferr100, it is necessary to revise the initial diagnosis.

Calculation of a dose for completion of content of iron after blood loss or delivery of autologous blood:

  The drug Likferr100 dose necessary for compensation of deficit of iron is counted on the following formula:

-   If the amount of the lost blood is known: intravenous administration of 200 mg of iron (= 10 ml of the drug Likferr100) leads to the same increase in concentration of Hb, as well as transfusion of 1 unit of blood (= 400 ml with concentration of Hb of 150 g/l).

Amount of iron which needs to be filled (mg) = quantity of units of the lost blood x 200 or the necessary volume of the drug Likferr100 (ml) = quantity of units of the lost blood x 10.

-   At decrease in maintenance of Hb: use the previous formula provided that the depot of iron is not required to be filled up.

Amount of iron which needs to be filled with [mg] = the body weight [kg] x 0,24 x (a normal indicator of Hb - the patient's Hb) (g/l),

For example: body weight is 60 kg, deficit of Hb=10 of g/l - necessary amount of iron =   150 mg, the necessary volume of the drug Likferr100 = 7,5 ml

Treatment of the patients with chronic renal diseases who are on a hemodialysis and receiving additional treatment by erythropoetin.

The drug is administered strictly intravenously. The injection has to be carried out as it is possible more slowly, duration of introduction increases in process of increase in a dose. The procedure does not represent special complexity for hemodialysis patients as they usually have a suitable intravenous access. The drug is administered in 0,9% chloride sodium solution within not less than 15 min. within 2 last hours of a session of a hemodialysis.

Absolute deficit of iron (phase of correction of anemia):
30–50 mg an iron/session of dialysis or 1000 mg of iron within 6–10 weeks.
Phase of a maintenance therapy

Various doses, in various modes are appointed:
10–25 mg an iron/session of dialysis or 100 mg of iron / once a month (depending on concentration of ferritin of serum).
Phase of correction of hemoglobin of 150 mg of iron for increase in concentration on 10 g/l.

Features of use:

It is necessary to observe strictly drug Likferr100 rate of administering (at bystry administration of drug the ABP can decrease). Higher frequency of development of undesirable side reactions (in particular - decrease in the ABP) including heavy, is associated with increase in a dose. Thus, time of administration of drug given in the section "Route of Administration and Doses" has to be observed strictly even if the patient does not receive drug in the most tolerable single dose.

 During administration of the drug Likferr100 it is necessary to control hemodynamics parameters.

 Likferr100 it has to be appointed only that patient at whom the diagnosis of anemia is confirmed with the corresponding datas of laboratory (for example, results of definition of ferritin of serum or indicators of hemoglobin and a hematocrit, quantity of erythrocytes and their parameters - the average volume of an erythrocyte or average content of hemoglobin in an erythrocyte).

 Intravenous iron preparations can cause allergic or anaphylactoid reactions which can be potentially life-threatening. Patients with bronchial asthma, eczema, atopic diseases, a polyvalent allergy, allergic reactions to other iron preparations, and also the faces having low iron-binding ability of serum / or insufficiency of folic acid, have the increased risk of development of allergic or anaphylactoid reactions (see the section "With Care").

 The researches conducted at the patients having hypersensitivity reactions to an iron dextran showed lack of complications against the background of treatment by drug.

 It is necessary to avoid penetration of drug into perivenous space since hit of Likferra100 out of limits of a vessel leads to a necrosis of fabrics and brown coloring of skin. In case of development of this complication, it is recommended (if the needle still is in a vessel) to enter a small amount of 0,9% of solution of sodium of chloride. For acceleration of removal of iron and prevention of its further penetration into surrounding fabrics, drawing to the place of an injection heparin - the containing drugs is recommended (gel or ointment are applied the easy movements, without rubbing).

Administration of drug in the presence of a deposit is inadmissible.

 Contains in 1 ml of the drug Likferr100 from 260 mg to 340 mg of sucrose. These data need to be considered at patients with a diabetes mellitus. At drop maintaining drug depending on indications the most tolerable single dose can reach 500 mg of iron that corresponds to introduction of 8,5 g of sucrose. At recalculation of this amount of carbohydrates in the grain units (GU) (1 XE = 12 g of carbohydrates), it corresponds to 0,7 XE.

During therapy by erythrogenesis stimulators exchange of iron is controlled by means of such indicators as concentration of ferritin of serum and the transferrin saturation by iron (TSI). Determination of quantity of hypochromia erythrocytes and concentration of hemoglobin in reticulocytes helps to make the decision on need of purpose of iron preparations intravenously when there is a giperferritinemiya and low NTZh. The risk of an overload iron is compensated by blood losses during the procedures connected with dialysis (1-3 g of iron a year are lost). It is necessary to control concentration of ferritin of serum regularly. Concentration of ferritin of serum is higher than 500 mkg/l (at a normal indicator of S-reactive protein), remaining a long time, can testify to an iatrogenic overload iron. In such cases iron preparations should be cancelled (therapy by stimulators of an erythrogenesis has to continue). Because iron stimulates growth of the majority of microorganisms, iron preparations should be cancelled at development of acute bacterial infections. Also therapy by iron preparations intravenously has to be carried out with precaution at patients with permanent dialysis catheters.

Features of influence of drug on ability to manage the vehicle or during the work as potentially dangerous mechanisms

 Safety of use of drug on ability to manage the vehicle or potentially dangerous mechanisms is not established. It is recommended to be careful when driving or during the work with potentially dangerous mechanisms.

Side effects:

From the central nervous system: dizziness, headache, loss of consciousness, paresthesias.

 From cardiovascular system: heartbeat, tachycardia, decrease in the ABP, kollaptoidny states, feeling of heat, "inflows" of blood to the person, peripheral hypostases.

 From respiratory system: bronchospasm, asthma.

 From the alimentary system: passing flavoring disturbances (in particular, "metal" smack in a mouth), diffuse abdominal pains, pain in epigastric area, diarrhea, a food faddism, nausea, vomiting.

 From integuments: erythema, itch, rash, pigmentation disturbance, increase in perspiration.

 From a musculoskeletal system: arthralgia, dorsodynia, hypostasis of joints, mialgiya, extremity pain.

 Allergic reactions: anaphylactoid reactions, face edema, throat hypostasis.

 Others: an adynamy, a stethalgia, to back, feeling of weight in breasts, weakness, feeling of an indisposition, pallor, fervescence, a fever.

Local reactions: pain and hypostasis in an injection site (especially at ekstravazalny hit of drug), phlebitis, a burning sensation, a hematoma.

 If any of the side effects specified in the instruction are aggravated, or you noticed any other side effects which are not specified in the instruction, report about it to the doctor.

Interaction with other medicines:

Co-administration of the drug Likferr100 with dosage forms of iron for intake as absorption of iron from digestive tract decreases is not admissible. Treatment by peroral iron preparations can be begun not earlier than in 5 days after the last injection.

Likferr100 it is possible to mix in one syringe only from 0,9% chloride sodium solution. No other solutions for intravenous administration and therapeutic drugs are allowed to be added as there is a risk of precipitation and/or other pharmaceutical interaction. Compatibility with containers from other materials, than glass, polyethylene and polyvinylchloride is not studied.

If you accept other drugs, it is necessary to consult with the doctor.

Contraindications:

Hypersensitivity to drug Likferr100 components;
the anemia which is not connected with deficit of iron;
existence of signs of an overload iron (hemosiderosis, hemochromatosis) or disturbance of process of its utilization;
The I trimester of pregnancy (see the section "Use at Pregnancy and during Breastfeeding").

With care

 At patients with bronchial asthma, eczema, polyvalent allergy, allergic reactions to other parenteral iron preparations (in connection with high risk of development of allergic reactions (see the section "Special Instructions")). Also care is required at introduction of iron preparations to patients with a liver failure, with acute infectious diseases and to the persons having low iron-binding ability of serum and/or deficit of folic acid, a diabetes mellitus (see the section "Special Instructions"), to patients of children's age (up to 18 years) (in connection with insufficiency of data on safety and efficiency).

 Use at pregnancy and during breastfeeding.

 Drug is contraindicated in the I trimester of pregnancy. In II and III trimesters of pregnancy apply only if the estimated advantage for mother exceeds potential risk for a fruit. In the period of a lactation safety of use of drug is not established. It is recommended to stop breastfeeding (in need of drug use) or to cancel drug.

Overdose:

Symptoms: decrease in the ABP (symptoms of a collapse are shown within 30 min.), hemosiderosis symptoms. Treatment: symptomatic, if necessary – the medicines connecting iron (helator), for example Deferoxaminum.

Storage conditions:

At a temperature not above 25 °C. Not to freeze. To store in the place, unavailable to children. Period of validity: 3 years. Not to use after the period of validity specified on packaging.

Issue conditions:

According to the recipe

Packaging:

Solution for intravenous administration of 20 mg/ml.

On 5 ml in ampoules of light-protective glass. On 5 ampoules in the plastic pallet. On 1 plastic pallet together with the application instruction in a pack from a cardboard.