Argeferr - instructions for use, doses, side effects, contraindications

Pharmacodynamics: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 the 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 - 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 is partially retained in the form of ferritin after complexation with the protein ligand-apopherritin of liver mitochondria. The hemoglobin index rises more quickly and with greater certainty than after therapy with drugs containing iron (II).Introduction 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 the drug, the maximum concentration of iron (on average 538 μmol) in the blood is reached 10 minutes after the injection. The elimination half-life is 6 hours. The distribution volume in the equilibrium state is approximately 8 liters, which indicates a low distribution of iron in body fluids. The excretion of iron by the kidneys observed in the first 4 hours after administration is less than 5% of the total clearance. After 24 hours, the serum iron concentration returns to its original (before administration) value and about 75% 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:

The use of the drug is contraindicated in the event that:

Anemia is not associated with iron deficiency;
There are signs of iron overload (hemosiderosis, hemochromatosis) or disruption of the process of its utilization;
there is an increased sensitivity to Argeferr ® or its components;
I trimester of pregnancy (see section "Use during pregnancy and lactation").

Carefully:

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")). Also, caution is 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 ( up to 18 years) (due to insufficient safety and efficiency data).

Pregnancy and lactation:

Argeferr® is contraindicated in the first trimester of pregnancy. In II and III trimesters of pregnancy the drug is prescribed in the case,if the expected effect of the application exceeds the possible 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:

Argeferr ® is administered only intravenously (slowly by jet or drip), as well as into the venous portion of the dialysis system, and is not intended for intramuscular administration. Impossible simultaneous introduction of the full therapeutic dose of the drug.

Before the introduction of the first therapeutic dose, a test dose should be administered. If during the period of observation there were phenomena of intolerance, the administration of the drug should be immediately turned.

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

Drip introduction:

Argeferr® is preferable to inject with droplet infusion in order to reduce the risk of a pronounced decrease in blood pressure and the risk of getting the solution into the circumveneous area.Immediately prior to infusion, the Argeferr ® preparation should be diluted with 0.9% sodium chloride solution in a ratio of 1:20 [eg, 1 ml (20 mg 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 droplet administration of the therapeutic dose of the drug, a test dose should be administered: 1 ml of the preparation (20 mg) of iron to adults and children weighing more than 14 kg and half the daily dose (1.5 mg iron / kg) for children weighing 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:

Argeferr ® can also be administered as a dilute solution intravenously slowly, at a rate of 1 ml of Argeferr ® (20 mg iron) per minute (for example, 5 ml of Argeferr ® (100 mg of iron) is administered for 5 minutes).The maximum volume should not exceed 10 ml of Argeferr ® preparation (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 administration of the therapeutic dose of Argeferr®, a test dose should be administered: 1 ml of Argeferr® (20 mg iron) to adults and children weighing more than 14 kg, and half the daily dose (1.5 mg iron / kg) for children , having a body weight of 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 the injection, the patient is recommended to fix his hand for a while in the extended position.

Introduction to the dialysis system:

Argeferr® can be injected directly into the venous site of the dialysis system, strictly following the rules described for intravenous injection.

Calculation of dose:

The dose is calculated individually according to the total iron deficiency in the body according to the 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: Hb in norm = 130 g / l, the amount of deposited iron = 15 mg / kg of body weight.

For patients with a body weight of more than 35 kg: Hb in norm = 150 g / l, the amount of deposited iron = 500 mg.

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

The total volume (cumulative therapeutic dose) of the Argeferr ® preparation, which must be administered (in ml) to compensate for iron deficiency in the body is: Total iron deficiency (mg)/20 mg / ml.

Body weight [kg]	Cumulative therapeutic dose of Argeferr ® for administration:
	Hb 60 g / l		Hb 75 g / l		Hb 90 g / l		Hb 105 g / l
	mg Fe¹	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

¹Fe - iron

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

Standard dose:

Adults, including elderly (over 65 years) patients: 5-10 ml of Argeferra ® (100-200 mg of iron) 1-3 times a week, depending on the level of hemoglobin.

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 Argeferr ® (3 mg of iron) per kg of body weight 1-3 times a week, depending on the level of hemoglobin.

Maximum tolerable single dose:

Adults, including elderly (over 65 years) patients:

For ink-jet administration: 10 ml of Argeferr ® preparation (200 mg of iron), duration of administration is not less than 10 minutes.
For drip administration: 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.

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 starting treatment with Argeferr ® does not improve the hematologic parameters, it is necessary to revise the initial diagnosis.

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

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

The dose of Argeferr ®, 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 Argeferr ®) leads to 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 required volume of Argeferr® preparation (ml) = number of units of lost blood x10

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 (Hb fine - Hb patient) (g / l),

For example: body weight 60 kg, deficit Hb = 10 g / l => necessary amount of iron ≈ 150 mg => necessary volume of the preparation Argeferr® = 7.5 ml

Treatment of patients with chronic kidney disease, who are on hemodialysis and receive additional treatment with erythropoietin

The drug is administered strictly intravenously. Injection is carried out as slowly as possible, the duration of administration increases as the dose increases. The procedure is not particularly difficult for patients on hemodialysis, since they usually have suitable intravenous 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 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:

Currently, there are known about the following undesirable phenomena that have a temporary and possible causal relationship to the administration of Argeferr®. All the symptoms were very rare (incidence less than 0.01% and greater than or equal to 0.001%).

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

From the cardiovascular system: heart palpitations, tachycardia, lowering of arterial pressure, collapsoid states, sensation of fever, "tides" of blood to the face, peripheral edema.

On the part of the respiratory system: bronchospasm, shortness of breath.

From the gastrointestinal tract: diffuse pain in the abdomen, pain in the epigastric region, diarrhea, taste distortion, nausea, vomiting, transient taste sensations (in particular, "metallic" taste in the mouth).

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.

From the immune system: allergic, anaphylactoid reactions, including facial edema, laryngeal edema.

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

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

Overdose:

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

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

Interaction:

The drug should not be administered simultaneously with the medicinal forms of iron for oral administration, as it helps to reduce the absorption of iron from the gastrointestinal tract. Treatment with oral iron preparations can begin no earlier than 5 days after the last injection.

Argeferr ® 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

Special instructions:

Argeferr® should be given only to those patients who have confirmed the diagnosis of anemia with appropriate laboratory data (for example, serum ferritin or hemoglobin and hematocrit determination results, the number of red blood cells and their parameters-the mean erythrocyte volume or the mean hemoglobin content in the erythrocyte). Intravenous iron preparations can cause allergic or anaphylactoid reactions, which can be potentially life threatening.

It should be strictly observed the rate of administration of the drug Argeferr® (with rapid administration of the drug, blood pressure may decrease). A higher incidence of side effects (in particular - lowering blood pressure), including severe, is associated with an increase in dose.Thus, the time of administration of the drug, given in the section "Methods of administration and dose", should be strictly observed, even if the patient does not receive the drug in the maximum tolerable single dose.

During the period of administration of Argeferr ®, it is necessary to control parameters of hemodynamics.

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 conducted in patients with hypersensitivity reactions 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 ingress of Argeferra® 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 lightly without rubbing).

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

In 1 ml of the preparation Argeferr ® contains from 260 to 340 mg of sucrose. These data should be taken into account in patients with diabetes mellitus. With the drip administration of the drug, depending on the indications, the maximum tolerable single dose can reach 500 mg of iron, which corresponds to the administration 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 monitored by means of such parameters as serum ferritin concentration and saturation with iron transferrin (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 the erythropoiesis stimulant 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 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 is not 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 of the drug in ampoules of hydrolytic dark glass (type 1, USP). On the ampoule, the breakage ring and the identification ring are marked.

For 5 ampoules in a polyvinyl chloride outline pack together with the instructions for use are placed in a cardboard box.

For 25 ampoules, together with the instructions for use are placed in a cardboard box.

Packaging:

5 ml of the drug in ampoules of hydrolytic dark glass (type 1, USP). On the ampoule, the breakage ring and the identification ring are marked.

For 5 ampoules in a polyvinyl chloride outline pack together with the instructions for use are placed in a cardboard box.

For 25 ampoules, together with the instructions for use are placed in a cardboard box.

Storage conditions:

In the dark place at a temperature of 4 to 25 ° C. Do not freeze.

Keep out of the reach of children.

Shelf life:

2 years.

Do not use the product after the expiry date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LSR-008788/10

Date of registration:26.08.2010

The owner of the registration certificate: Genfa Medica S.A. Genfa Medica S.A. Switzerland

Manufacturer: & nbsp

GENFA MEDICA, S.A. Switzerland

Representation: & nbspHEAD OF MEDICA SAHEAD OF MEDICA SASwitzerland

Information update date: & nbsp26.08.2010

Illustrated instructions

Instructions

Argeferr (Argeferr)