Likferr100 - instructions for use, dose, side effects, contraindications

The drug iron, regulates metabolic processes. It is a colloidal solution, which consists of spheroidal iron-carbohydrate nanoparticles.In the core (center) of each particle is iron [III] hydroxide. The core is surrounded by a shell of sucrose, which stabilizes iron [III] hydroxide, slowly releases bioactive iron and stores the resulting particles in a colloidal solution. As a result, a complex is formed, the molecular mass of which is approximately 43 kD, as a result of which its excretion through the kidneys in an unchanged form is impossible. Iron [III] in this complex is associated with structures similar to natural ferritin. The active substance of the preparation of iron [III] hydroxide, the sucrose complex, when ingested, dissociates into iron and sucrose in the reticuloendothelial system. Due to the lower stability of iron, sugar compared with transferrin, there is a competitive exchange of iron in favor of transferrin. As a result, about 31 mg of iron is transferred within 24 hours. Polycyclic iron hydroxide [III] is partially retained in the form of ferritin after complexation with the protein ligand - apoferritin of liver mitochondria. The hemoglobin index rises more quickly and with greater certainty than after therapy with drugs containing iron [II].The introduction of 100 mg of iron [III] leads to an increase in hemoglobin by 2-3 %; in pregnancy - by 2%. The toxicity of the drug is very low. The therapeutic index is 30 (200/7).

Pharmacokinetics:

After a single intravenous injection of Likferr100® containing 100 mg of iron, the maximum concentration of iron (on average 538 μmol) is reached 10 minutes after the injection. Half-life is 6 hours. The volume of distribution in the equilibrium state is approximately 8 liters, which indicates a low distribution of iron in the liquid media of the body.

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

Indications:

iron deficiency (including iron deficiency and acute posthemorrhagic anemia) in patients with the need for rapid iron replenishment;
in patients who do not tolerate oral iron preparations;
the presence of diseases of the gastrointestinal tract (GIT), in which oral iron preparations can not be used.

Contraindications:

hypersensitivity to the components of the drug Lycferr100®;
anemia not related to iron deficiency;
presence of signs of iron overload (hemosiderosis, hemochromatosis) or disruption of its utilization;
I trimester of pregnancy (see section "Application during pregnancy and during breast-feeding").

Carefully:

In patients with bronchial asthma, eczema, polyvalent allergy, allergic reactions to other parenteral iron preparations (due to a high risk of allergic reactions (see section "Special instructions")).

Caution is also required when administering iron preparations to patients with hepatic insufficiency, diabetes mellitus (see section "Special instructions"), with acute infectious diseases and persons with low serum iron binding capacity and / or folic acid deficiency, in children under 18 ) (due to insufficient data on safety and effectiveness).

Pregnancy and lactation:

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

During lactation, the safety of the drug is not established. It is recommended to stop breastfeeding (if necessary, use the drug) or to cancel the drug.

Dosing and Administration:

Introduction

Likferr100 is injected only intravenously - slowly by jet or drip, as well as into the venous section of the dialysis system and is not intended for intramuscular injection. Impossible one-stage introduction of the full (cumulative) therapeutic dose of the drug

Before the introduction of the first therapeutic dose, it is necessary to prescribe a test dose. If during the observation period there were intolerance phenomena, the drug should be discontinued immediately. Before opening, the ampoule should be inspected for possible sediment and damage. You can use only a brown solution without sediment.

Drip introduction

Likferr100 is preferable to inject during drip infusion in order to reduce the risk of pronounced reduction in blood pressure (BP) and the risk of getting the solution into the circumveneous area. Directly before infusion, Lycferr100 should be diluted 0.9 % solution of sodium chloride 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 introduced at the following rate: 100 mg of iron - not less than 15 minutes; 200 mg of iron - for 30 minutes; 300 mg of iron - for 1.5 hours; 400 mg of iron - for 2.5 hours; 500 mg of iron - for 3.5 hours. The maximum tolerated single dose of 7 mg iron / kg body weight should be administered for a minimum of 3.5 hours, regardless of the total dose of the drug.

Before the first dropping of the therapeutic dose of Lycferr100, a test dose should be administered: 1 ml of Lycferr100 (20 mg of iron) to adults and children weighing more than 14 kg and half of the daily dose (1.5 mg of iron / kg) to children with body weight less than 14 kg for 15 minutes. In the absence of adverse events, the rest of the solution should be administered at the recommended rate.

Inkjet introduction

Likferr100 preparation can also be administered as a dilute solution intravenously slowly, at a rate of 1 ml of Likferr100 (20 mg iron) per minute (for example, 5 ml of Likferr100 (100 mg of iron) is injected for 5 minutes). The maximum volume of the drug should not exceed 10 ml of the preparation Likferr100 (200 mg of iron) per injection.

After injection, the patient is recommended to lock his hand for a while in the extended position.

Before the first jet injection of the therapeutic dose of Lycferr100, a test dose should be administered: 1 ml of Likferr100 (20 mg of iron) to adults and children weighing more than 14 kg and half the daily dose (1.5 mg of iron / kg) to children with body weight 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 injection, the patient is recommended to fix his arm in an extended position.

Introduction to the dialysis system

Likferr100 can be injected directly into the venous section of the dialysis system, strictly following the rules described for intravenous injection.

Calculation of dose

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

Total iron deficiency (mg) = body weight (kg) x (Hb fine - Hb patient (g / l)) x 0.24 + deposited iron (mg)

For patients with a body weight of less than 35 kg:

- the amount of deposited iron = 15 mg / kg body weight,

- normal rate Hb = 130 g / l.

For patients with a body weight of more than 35 kg:

- the amount of deposited iron = 500 mg,

- normal rate Hb = 150 g / l.

Coefficient 0.24 = 0.0034 x 0.07 x 1000 (iron content in hemoglobin = 0.34%, blood volume = 7 % of body weight; coefficient 1000 = transfer from "g" to "mg").

Then you should calculate the cumulative (course) dose of Likferr100, which will need to be introduced to compensate for iron deficiency in the body according to the following formula:

The total volume of the preparation (in ml) = Total iron deficiency (mg) / 20 mg / ml The approximate values of the total iron deficiency and the total volume of the drug for introduction to the course of therapy are given in the table:

Total volume of Likferr100 preparation for treatment

Body weight (kg)	The cumulative (course) therapeutic dose of Lycferr100 for administration:
Body weight (kg)	Hb 60 g / l			Hb 75 g / l			Hb 90 g / l			Hb 105 g / l
	mg Fe		ml	mg Fe		ml	mg Fe	ml		mg Fe	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

Multiplicity of administration is determined by the doctor, but not more often than every other day.

Adults, including elderly (over 65 years) patients: 5-10 ml 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 inject no more than 0.15 ml of Lycferr100 (3 mg of iron) per kg of body weight 1-3 times a week, depending on the indicator Hb.

The maximum tolerable single dose (adults, including the elderly (over 65 years) patients):

For inkjet insertion: 10 ml of the preparation Likferr100 (200 mg of iron), the duration of administration is not less than 10 minutes.

For drip introduction: 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.

Typically, large doses are associated with a higher incidence of adverse events.

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

If, 1-2 weeks after the beginning of treatment with Lycferr 100, there is no improvement in hematological parameters, the initial diagnosis should be reviewed.

Calculation of the dose for replenishing the iron content after blood loss or autologous blood donation:

The dose of Likferr100, needed to compensate for iron deficiency, is calculated by the following formula:

If the amount of blood lost is known: intravenous administration of 200 mg of iron (= 10 ml of Lycferr100 preparation) results in the same increase in concentration Hb, as well as transfusion of 1 unit of blood (= 400 ml with concentration Hb 150 g / l).

The amount of iron that must be replenished (mg) = number of units of lost blood x 200 or necessary volume of the drug Likferr100 (ml) = number of units of lost blood x 10.

- With a decrease in content Hb: Use the previous formula, provided that the iron depot is not required to replenish.

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

For example: body weight 60 kg, deficit Hb=10 g / l - the required amount of iron 150 mg, the required volume of the drug Likferr100 = 7.5 ml

Treatment of patients with chronic renal diseases who are on hemodialysis and receiving additional treatment with erythropoietin.

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

Absolute iron deficiency (anemia correction phase):

- 30-50 mg iron / dialysis session or

- 1000 mg of iron for 6-10 weeks.

Supportive therapy phase

Assign different doses, in different modes:

- 10-25 mg 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 the concentration by 10 g / l.

Side effects:

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

From the cardiovascular system: palpitations, tachycardia, decreased blood pressure, collapsoid conditions, a feeling of heat, "flushes" of blood to the face, peripheral edema.

From the respiratory system: bronchospasm, shortness of breath.

From the digestive system: transient flavors (in particular, "metallic" taste in the mouth), diffuse abdominal pain, epigastric pain, diarrhea, taste distortion, nausea, vomiting.

From the skin: erythema, pruritus, rash, impaired pigmentation, increased sweating.

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

Allergic reactions: anaphylactoid reactions, edema of the face, swelling of the larynx.

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

Local reactions: pain and swelling at the injection site (especially with an extravasal drug), phlebitis, a burning sensation, a hematoma.

If any of the side effects listed in the manual are aggravated, or if you notice any other side effects not listed in the instructions, inform the doctor about it.

Overdose:

Symptoms: a decrease in blood pressure (signs of collapse occur within 30 minutes), symptoms of hemosiderosis.

Treatment: symptomatic, if necessary - drugs that bind iron (chelators), for example, deferoxamine.

Interaction:

It is not permissible simultaneous administration of the preparation Likferr100 with medicinal forms of iron for oral administration, as the absorption of iron from the gastrointestinal tract decreases. Treatment with oral iron preparations can begin no earlier than 5 days after the last injection.

Likferr100 can be mixed in one syringe only with 0.9% sodium chloride solution. No other solutions for intravenous administration and therapeutic agents are added, since there is a risk of precipitation and / or other pharmaceutical interactions.Compatibility with containers of other materials than glass, polyethylene and polyvinyl chloride has not been studied.

If you take other drugs, it is necessary to consult a doctor.

Special instructions:

It is necessary to strictly adhere to the rate of administration of the drug Lycferr100 (with rapid administration of the drug, blood pressure can decrease). A higher incidence of undesirable adverse reactions (in particular, lowering blood pressure), including severe ones, is associated with an increase in the dose. Thus, the time of administration of the drug, given in the section "Dosing and Administration", should be strictly observed, even if the patient does not receive the drug in the maximum tolerated single dose.

During the introduction of the drug Likferr100 it is necessary to monitor the parameters of hemodynamics.

Likferr100 should be administered only to those patients whose diagnosis of anemia is confirmed by appropriate laboratory data (for example, serum ferritin determination results or hemoglobin and hematocrit indicators, the number of erythrocytes and their 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 allergy, allergic reactions to other iron preparations, as well as those having low iron binding capacity of serum / or folic acid deficiency have an increased risk of allergic or anaphylactoid reactions (see. The section "Precautions" ). Studies carried out in patients with increased sensitivity to iron dextran, showed no complications on the background of drug treatment.

It is necessary to avoid penetration of the drug into the circumveneous area, because the penetration of Lycferra 100 beyond 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 introduce a small amount of 0.9% sodium chloride solution. To accelerate the excretion of iron and prevent its further penetration into surrounding tissues, it is recommended to apply to the injection site of heparin-containing drugs (gel or ointment is applied by the lungsmovements, not rubbing). It is inadmissible to administer the drug in the presence of sediment.

In 1 ml of the preparation Likferr100 contains from 260 mg to 340 mg of sucrose. These data should be taken into account in patients with diabetes mellitus. Drip administration of the drug, depending on the indications, the maximum tolerable single dose can reach 500 mg of iron, which corresponds to the introduction of 8.5 g of sucrose. When recalculating a given amount of carbohydrates into grain units (XE) (1 XE = 12 g carbohydrates), it corresponds to 0.7 XE.

During therapy with stimulants of erythropoiesis, iron metabolism is controlled by such parameters as serum ferritin concentration and iron transferrin saturation (NTZ). Determination of the number of hypochromic erythrocytes and hemoglobin concentration in reticulocytes helps to decide whether to prescribe iron preparations intravenously, when there is hyperfertinemia and low NTH. The risk of iron overload is compensated for by blood loss during procedures associated with dialysis (1-3 grams of iron per year are lost). The concentration of serum ferritin should be monitored regularly. The concentration of serum ferritin above 500 μg / l (with a normal C-reactive protein), which persists for a long time, may indicate iatrogenic iron overload.In such cases, iron preparations should be discontinued (therapy with stimulants of erythropoiesis should continue). Due to the fact that iron stimulates the growth of most microorganisms, iron preparations should be abolished when developing acute bacterial infections. Also, iron therapy with intravenous drugs should be performed with caution in patients with permanent dialysis catheters.

Effect on the ability to drive transp. cf. and fur:The safety of the drug on the ability to drive a vehicle or potentially dangerous mechanisms has not been established. It is recommended to use caution when driving a vehicle or when working with potentially dangerous machinery.

Form release / dosage:

Solution for intravenous administration of 20 mg / ml.

5 ml per ampoule of light-protective or colorless glass.

For 5 ampoules in a contoured cell package with a lid integral of a film of PVC or without a lid.

1 contour pack together with instructions for use in a pack of cardboard.

3 ampoules in a contoured cell pack of a polyvinyl chloride or polyethylene terephthalate film or a polystyrene tape.

1, 2 or 8 contour mesh packages together with instructions for use in a pack of cardboard.

5 ml in bottles of colorless glass, sealed with rubber stoppers and crimped with aluminum caps, equipped with plastic caps with an inscription in English "FLIP OFF" or without an inscription.

1 bottle with instructions for use in a pack of cardboard.

3 or 5 bottles in a cardboard stand together with instructions for use in a pack of cardboard.

Packaging:

5 ml per ampoule of light-protective or colorless glass.

For 5 ampoules in a contoured cell package with a lid integral of a film of PVC or without a lid.

1 contour pack together with instructions for use in a pack of cardboard.

3 ampoules in a contoured cell pack of a polyvinyl chloride or polyethylene terephthalate film or a polystyrene tape.

1, 2 or 8 contour mesh packages together with instructions for use in a pack of cardboard.

5 ml in bottles of colorless glass, sealed with rubber stoppers and crimped with aluminum caps, equipped with plastic caps with an inscription in English "FLIP OFF" or without an inscription.

1 bottle with instructions for use in a pack of cardboard.

3 or 5 bottles in a cardboard stand together with instructions for use in a pack of cardboard.

Storage conditions:

At a temperature of no higher than 25 ° C. Do not freeze.

Keep out of the reach of children.

Shelf life:

The solution for intravenous administration in ampoules is 3 years.

Solution for intravenous administration in vials - 2 years.

Do not use after the expiration date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LSR-008006/10

Date of registration:12.08.2010

The owner of the registration certificate:FarmSirma Soteks, ZAO FarmSirma Soteks, ZAO Russia

Manufacturer: & nbsp

FarmSirma Soteks, ZAO Russia

Representation: & nbspPharm Company Sotex CJSC Pharm Company Sotex CJSC Russia

Information update date: & nbsp23.05.2014

Illustrated instructions

Instructions

Likferr100® (Likferr 100®)