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

The drug iron, regulates metabolic processes. Multi-nuclear centers of iron [III] hydroxide are surrounded from the outside by a multitude of non-covalently bound sucrose molecules. 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 the natural ferritin protein (physiological iron depot).

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 preserved 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]. Introduction 100 mg gland [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:

Ferrokinetics of iron-sucrose complex labeled ⁵²Fe and ⁵⁹Fe, was evaluated in patients with anemia and chronic renal failure. During the first 6-8 hours ⁵²Fe was captured by the liver, spleen and bone marrow. It is believed that the capture of the radioactive label by the spleen, rich in macrophages, is typical for the capture of iron by the reticuloendothelial system.

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

Half-life is 6 hours. After the administration of the preparation, sucrose basically disintegrates, and the multinuclear iron-containing nucleus is mainly captured by the reticuloendothelial system of the liver, spleen, and bone marrow. At 4 weeks after the administration, iron utilization by erythrocytes is from 59% to 97%.

The average molecular weight of the iron-sucrose complex is approximately 43 kDa, which is large enough to prevent excretion through the kidneys.Excretion of iron by the kidneys within the first 4 hours after the administration of a dose of the drug containing 100 mg of iron is less than 5% of the total clearance. After 24 hours, the serum iron content returns to its original (before administration) value. The excretion of saccharose by the kidneys is approximately 75% of the administered dose.

Indications:

Iron deficiency (including iron deficiency and acute posthemorrhagic anemia) in the following cases:

- if necessary to quickly fill iron deficiency;

- in patients who do not tolerate oral iron preparations or do not follow the treatment regimen;

- in patients with active inflammatory bowel diseases, in which oral iron preparations are ineffective.

Contraindications:

- Hypersensitivity to iron sugars complex, solution of iron-sucrose complex or to any of the components of the preparation;

- anemia not related to iron deficiency;

- presence of signs of iron overload (hemosiderosis, hemochromatosis) or disruption of its utilization;

- I trimester of pregnancy and the period of breastfeeding (see section "Application during pregnancy and during breast-feeding").

Carefully:

Caution is required when using iron preparations:

- in patients with bronchial asthma, eczema, polyvalent allergy, allergic reactions to other parenteral iron preparations (due to the high risk of allergic reactions [see "Cautions".]);

- in patients with a low serum iron binding ability and / or folic acid deficiency;

- in patients with hepatic insufficiency;

- in patients with acute or chronic infectious diseases;

- in patients with elevated serum ferritin content;

- in patients with diabetes mellitus (see section "Special instructions");

- in patients of children (under 18 years of age) due to insufficient data on safety and efficacy.

Pregnancy and lactation:

The drug Wialfer is contraindicated in the first trimester of pregnancy. A moderate amount of data on the use of iron [III] preparations of the hydroxide of the sucrose complex in the II and III trimesters of pregnancy did not reveal any threats to the mother and newborn. Nevertheless, in the II and III trimesters of pregnancy, the drug is only possible if the intended benefit to the mother exceeds the potential risk to the fetus.

The results of the animal study did not reveal any direct or indirect adverse effects of iron [III] hydroxide of the sucrose complex on the course of pregnancy, embryo / fetus development, childbirth or postnatal development.

Data on the release of iron with human breast milk after intravenous iron [III] hydroxide of the sucrose complex are limited. During the period of breastfeeding, the safety of the use of Vialfer is not established. It is recommended to stop breastfeeding (if necessary, use the drug) or to cancel the drug.

Dosing and Administration:

Introduction

Vialfer is administered only intravenously - slowly or driply, as well as into the venous section of the dialysis system and is not intended for intramuscular injection.

Before opening, the ampoule should be inspected for possible sediment and damage. You can use only a brown solution without sediment.

Each Vialpher ampoule is intended exclusively for single use. Any residues of unused medicinal product or its waste should be disposed of in accordance with local requirements.

The introduction of the drug Vialfer should be carried out under the supervision of medical personnel who have experience in the diagnosis and treatment of anaphylactic reactions, in the conditions of a specialized department. It should be possible to carry out anti-shock therapy, including a 0.1% solution of epinephrine (adrenaline), antihistamines and / or corticosteroid drugs. The test dose is not a reliable prognostic factor for the development of subsequent hypersensitivity reactions, and therefore its preliminary administration is not recommended.

During the administration of Viellfer and immediately after the administration, patients should be under the supervision of a physician. When the first signs of anaphylactic reactions appear, the drug should be discontinued immediately. It is necessary to observe each patient for at least 30 minutes after each administration of the drug Vialfer in a therapeutic dose for the absence of undesirable phenomena.

Intravenous drip introduction

The Vialfer preparation is preferably administered during a drip infusion in order to reduce the risk of a pronounced reduction in arterial pressuredanger getting the solution into the circumferential space.

Immediately before infusion, the drug should be diluted with 0.9% sodium chloride solution in a ratio of 1:20 [eg, 1 ml (20 mg of iron) in 20 ml of 0.9% sodium chloride solution]. The diluted solution should be clear, brown in color. Dilution of the drug to lower concentrations is unacceptable for reasons related to the stability of the solution.

The resulting solution is introduced as follows (Table 1):

Table 1.

The dose of iron (mg)	Amount of preparation Wialfer (ml)	The maximum volume of 0.9% solution of sodium chloride	The minimum infusion time
100 mg	5 ml	100 ml	15 minutes
200 mg	10 ml	200 ml	30 minutes
300 mg	15 ml	300 ml	1,5 hour
400 mg	20 ml	400 ml	2,5 hours
500 mg	25 ml	500 ml	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.

Intravenous injection

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

Introduction to the venous site of the dialysis system

The drug can be administered during the hemodialysis session directly to the venous site of the dialysis system, strictly following the rules described in the section "Intravenous injection".

Calculation of dose

The total cumulative dose of Viellfer is equivalent to the total iron deficiency and is determined based on the hemoglobin and body weight. Before the introduction, it is necessary to individually calculate for each patient the total iron deficiency in the body according to the Hanzoni formula:

Total iron deficiency [mg] = body weight [kg | x (Target hemoglobin content [g / l] - Actual hemoglobin content of patient [g / l]) x 0.24 * + deposited iron [mg]

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

the target hemoglobin content is 130 g / l;
amount of deposited iron = 15 mg / kg body weight.

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

target hemoglobin content = 150 g / l;
the amount of deposited iron = 500 mg,

^*Coefficient 0.24 = 0.0034 (iron content in hemoglobin = 0.34%) x 0.07 (blood mass ≈7% of body weight) x 1000 (factor 1000 = translation from [g] to [mg]).

Then it is necessary to calculate the cumulative (course) dose of the drug, which will need to be introduced to fill the iron deficiency in the body according to the following formula:

Total drug volume (in ml) = Total iron deficiency [mg] / 20 mg iron / ml

The approximate values of the total iron deficiency and the total volume of the Wialfer preparation for introduction to the course of therapy are given in Table 2:

Table 2. The total volume of Vialfer's preparation, depending on the body weight and the actual hemoglobin content

Body weight (kg)	The necessary cumulative (course) dose of the drug Vialfer (ml)
	Hemoglobin 60 g / l		Hemoglobin 75 g / l		Hemoglobin 90 g / l		Hemoglobin 105 g / l
	Fe [mg]	Rate of dose [ml]	Fe [mg]	Rate of dose [ml]	Fe [mg]	Rate of dose [ml]	Fe [mg]	Rate of dose [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

With a body weight of less than 35 kg, the target hemoglobin content is 130 g / l; With a body weight of 35 kg or more, the target hemoglobin content is 150 g / l;

In case the required cumulative (course) dose exceeds the maximum allowable single dose, it is recommended to divide the total dose of the drug into several administrations. Multiplicity of administration is determined by the doctor, but not more often than every other day.

If after 1-2 weeks after the beginning of treatment with the drug there is no response from hematological parameters, it is necessary to revise the initial diagnosis.

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

The dose of Viellfer, 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 the drug) leads to the same increase in hemoglobin concentration as the transfusion of 1 unit of blood (= 400 ml with a hemoglobin concentration of 150 g / l).

The amount of iron that must be replenished (mg) = The number of units of lost blood x 200 mg

The required volume of the drug (ml) = The number of units of lost blood x 10 ml.

If the hemoglobin content is below the desired: use the formula below (it is assumed 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 (Target hemoglobin [g / l] - Actual hemoglobin content of patient [g / l]).

Example: With a body weight of 60 kg and a decrease in hemoglobin content of 10 g / L

The necessary amount of iron = 60 x 0.24 x 10 ≈ 150 mg.

The required volume of the drug = 7.5 ml.

Standard doses

Adult patients and elderly patients (over 65):

5-10 ml of the preparation Vialfer (100 - 200 mg of iron) 1-3 times a week. The time of administration is indicated in the "Introduction" section above.

Children:

There are only limited data on the use of iron preparations [III] hydroxide of the sucrose complex in children. The experience of using the drug Vialfer in children is absent. In case of emergency, it is recommended to inject no more than 0.15 ml of the drug (3 mg of iron) per kg of body weight 1-3 times per week. The time of administration is indicated in the "Introduction" section above.

Maximum tolerated single and weekly dose

Adult patients and elderly patients

The maximum daily dose for jetting is not more than 3 times a week:

10 ml of Vialfer's preparation (200 mg of iron), the duration of administration is not less than 10 minutes.

The maximum daily dose for drip administration is not more often than 1 time per week:

Patients with a body weight of more than 70 kg: 500 mg of iron (25 ml of the preparation Vialfer), administered for a minimum of 3.5 hours;
Patients weighing 70 kg or less: 7 mg of iron per 1 kg of body weight, administered for a minimum of 3.5 hours.

The recommended infusion time outlined in the "Introduction" section should be strictly followed, even if the patient does not receive the maximum tolerated dose.

Side effects:

The most frequently recorded undesirable drug reactions are a change in taste sensations, arterial hypotension, pyrexia, chills, reactions at the injection site and nausea,which are registered in 0.5% -1.5% of patients receiving iron therapy [III] hydroxide of the sucrose complex. The most serious adverse reactions are hypersensitivity reactions.

The incidence of adverse events is determined according to the WHO classification of adverse drug reactions by frequency of occurrence: very often - ≥ 1/10 (≥ 10%); often - ≥ 1/100 and <1/10 (≥1% and <10%); infrequently - ≥ 1/1000 and <1/100 (≥0.1% and <1%); rarely - ≥1 / 10000 and <1/1000 (≥0.01% and <0.1%); very rarely - <1/10000 (<0.01%); an unknown frequency (it is impossible to determine the frequency of occurrence of an undesired reaction from available data).

Infections and infestations: rarely - pneumonia.

Violations from the blood and lymphatic system: infrequently polycythemia.

Immune system disorders: infrequently - hypersensitivity; unknown frequency - anaphylactoid reactions, angioedema, edema of the face, swelling of the larynx.

Metabolic and nutritional disorders: rarely - iron overload.

Impaired nervous system: often - transient violations of taste sensations (in particular, "metallic" taste in the mouth), distortion of taste; infrequently - headache dizziness, burning sensation, paresthesia, hypesthesia; rarely - a syncope, migraine,drowsiness; unknown frequency - reduced level of consciousness, confusion, loss of consciousness, anxiety, tremor.

Heart Disease: rarely - a feeling of palpitations; unknown frequency bradycardia, tachycardia.

Vascular disorders: often - lowering blood pressure, increasing blood pressure; infrequently - thrombophlebitis, phlebitis; rarely - hyperemia; unknown frequency - collapsoid states, thrombosis of superficial veins.

Disturbances from the respiratory system, chest and mediastinal organs: infrequently - shortness of breath; unknown frequency - bronchospasm.

Disorders from the gastrointestinal tract: often - nausea; infrequently - vomiting, abdominal pain, diarrhea, constipation; rarely - dry mouth.

Disturbances from the skin of the subcutaneous tissues: infrequently - itchy skin, skin rash; unknown frequency - hives, erythema, pigmentation disorders.

Disturbances from the musculoskeletal and connective tissue: infrequently - muscle cramps, myalgia, arthralgia, pain in the limbs, back pain; rarely - discomfort in the extremities, muscle spasms; unknown frequency - muscle hypotension.

Disorders from the kidneys and urinary tract: infrequently - chromaturia.

General disorders and disorders at the site of administration: often pain in the injection site; infrequent - chills, reactions at the injection site, extravasation at the injection site, discoloration of the skin at the injection site, burning sensation at the injection site, edema at the injection site, asthenia, fatigue, pain; rarely - a feeling of heat, chest pain, fever, itching at the injection site, bruising (bruising) at the injection site, excessive sweating, cold sweat, general malaise, pallor.

Laboratory and instrumental data: infrequently - increased activity of gamma-glutamyltransferase, increased activity of alanine aminotransferase, increased activity of aspartate aminotransferase, pathological changes in the results of "hepatic" samples; rarely - an increase in serum ferritin (as a consequence of an iron overdose or iron overload), an increase in the concentration of creatinine in the blood, an increase in lactate dehydrogenase activity in the blood.

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, tell your doctor.

Overdose:

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

Treatment: symptomatic, overdose should use drugs that bind iron (chelators) in accordance with standards of medical practice.

Interaction:

It is not permissible simultaneous administration of the drug 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.

The drug can be mixed in a single syringe with only 0.9% solution of sodium chloride.

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.

Special instructions:

Parenterally administered iron preparations can cause allergic or anaphylactoid reactions that can be potentially life-threatening,therefore, antiallergic drugs, and tEquipment for cardiopulmonary resuscitation and other necessitiessingle procedures. Hypersensitivity reactions were noted, incl. after the previous uncomplicated parenteral administration of iron preparations. After each injection of Wialfer, it is necessary to monitor each patient for at least 30 minutes for undesirable effects.

Patients with bronchial asthma (including anamnesis), eczema, other atopic diseases, polyvalent allergies, allergic reactions to other iron preparations, as well as individuals with low serum iron-binding capacity or folic acid deficiency, have an increased risk of developing allergic or anaphylactoid reactions (see the section "With caution"), and therefore the preparation of Viellfer in such patients should be used with caution.

Patients with impaired liver function parenteral iron preparations should be used only after a thorough assessment of the ratio of benefit and risk. Do not use iron drugs in patients with impaired liver function, if the latter are caused by iron overload.

In order to avoid overloading with iron, it is recommended to conduct a thorough monitoring of the iron content in the body. Vialfer should be administered only to those patients whose indications for use are confirmed by the results of appropriate laboratory tests (for example, ferritin content in the blood serum, transferrin saturation with iron, hemoglobin content, erythrocyte indices - mean erythrocyte volume [MCV] mean hemoglobin content in erythrocyte [MCH], mean hemoglobin concentration in erythrocyte mass [ICSU]).

Iron stimulates the growth of most microorganisms, and therefore parenteral iron preparations should be used with caution in acute and chronic infections. Patients with bacteremia are advised to stop using Vialfer. In patients with chronic infection, the benefit / risk ratio should be assessed before using the drug.

It is necessary to strictly adhere to the speed of administration of the drug (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 period of drug administration, it is necessary to monitor parameters of hemodynamics.

It is necessary to avoid penetration of the drug into the circumveneous area, because this can lead to the appearance of pain, inflammation, necrosis of the tissues and dyeing of the skin in brown. In case of unintentional administration of the drug to the paravernous space, treatment should be performed in accordance with the standards of medical practice.

In 1 ml of the drug 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. It is inadmissible to administer the drug in the presence of sediment.

From a microbiological point of view, the drug should be used immediately after opening the vial or diluting with a 0.9% solution of sodium chloride.

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, 20 mg / ml.

Packaging:

5 ml per ampoule of neutral colorless or dark glass (hydrolytic type 1) with a ring or break point. For each ampoule, a quick-fixing ink is printed or a label is attached.

5 ampoules in a plastic pallet, 1 plastic tray in a pack of cardboard along with instructions for use.

Storage conditions:

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

Keep out of the reach of children.

Shelf life:

3 years

Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LP-004038

Date of registration:22.12.2016

Expiration Date:22.12.2021

The owner of the registration certificate:VIAL, LLC VIAL, LLC Russia

Manufacturer: & nbsp

MEFAR ILAC SANAYII, A.S. Turkey

Representation: & nbspVIAL, LLCVIAL, LLC

Information update date: & nbsp09.01.2017

Illustrated instructions

Instructions

Wialfer (Vialfer)