FerMed - instructions for use, doses, 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 nucleus is surrounded by a shell of sucrose, which stabilizes the iron (III) hydroxide, slowly releases bi-active 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 is unchanged. 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 in the reticuloendothelial system into iron and sucrose. 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.

Hemoglobin rises faster 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%; during 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 FerMed, containing 100 mg of iron, the maximum concentration of iron (an average of 538 μmol) in the blood plasma is reached after 10 minutes after the injection. The 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 kidney, 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 the original (before administration) value, and about 75% sucrose leaves the vascular bed.

Indications:

- Iron deficiency conditions (including iron deficiency and acute posthemorrhagic anemia) in patients with the need for rapid iron replenishment;

- in patients who do not tolerate iron for oral administration;

- diseases of the gastrointestinal tract, in which the intake of iron preparation inside is not possible.

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 the preparation of FerMed or its inactive components;

- fructose intolerance and glucose / galactose absorption disorder or sucrose / isomaltase deficiency;

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

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 using iron preparations in patients with hepatic insufficiency, diabetes mellitus (see section "Special instructions"), with acute infectious diseases and in patients with low serum iron-binding capacity and / or folate deficiency, aged up to 18 years (due to insufficient data on safety and effectiveness).

Pregnancy and lactation:

Fermed is contraindicated in 1 trimester of pregnancy. In II and III trimesters of pregnancy the drug is prescribed if the expected benefit for the mother exceeds the potential risk to the fetus.

During the period of breastfeeding, 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:

Only for intravenous administration!

Introduction:

FerMed 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 one-stage introduction of the full (cumulative) therapeutic dose of the drug.

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

Drip introduction:

FerMed is preferably administered as a drip infusion in order to reduce the risk of a marked decrease in blood pressure and the risk of getting the solution into the circumveneous area.Immediately before infusion, the FerMed preparation should be diluted with 0.9% sodium chloride solution in a ratio of 1:20:

1 ml of solution for injection (equivalent to 20 mg of iron)	in 20 ml of 0.9% sodium chloride solution
5 ml of solution for injection (equivalent to 100 mg of iron)	in 100 ml of a 0.9% solution of sodium chloride
10 ml solution for injection (equivalent to 200 mg iron)	in 200 ml of a 0.9% solution of sodium chloride

The resulting solution is introduced at the following rate:

100 mg of iron	not less than 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

The maximum tolerated single dose of 7 mg iron / kg body weight should be maintained for a minimum of 3.5 hours, regardless of the total dose preparation.

Before the first dropping of the therapeutic dose of the drug, it is necessary to enter a test dose: 1 ml of the drug (20 mg) of iron for adults and children weighing more than 14 kg and half the daily dose (1.5 mg of 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:

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

After the injection, the patient needs to fix his hand in the extended position for some time.

Before the first jet administration of the therapeutic dose of FerMed, a test dose should be administered: 1 ml of FerMed (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 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.

Introduction to the dialysis system:

Fermed 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 in the norm - 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").

Then the cumulative (course) dose of the FerMed preparation should be calculated, which will need to be introduced to fill the 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 total iron deficiency and the total volume of the drug for introduction to the course of therapy are given in the table below:

Table. Total volume of FerMed for treatment

Body weight \| kg \|	The cumulative (course) therapeutic dose of FerMed for introduction:
	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

Fe -iron

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

Standard dose:

Adults, including elderly patients (over 65 years of age): 5-10 ml of the FerMed preparation (100-200 mg of iron) 1-3 times a week, depending on the Hb index.

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 FerMed (3 mg of iron) per kg of body weight 1-3 times a week, depending on the Hb value.

Maximum tolerable single dose (adults, including elderly patients (over 65 years of age)):

For inkjet insertion: 10 ml of FerMed preparation (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 of 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 the initiation of FERMED treatment, there is no improvement in hematologic parameters, the initial diagnosis should be reviewed. 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 FerMed, needed to compensate for iron deficiency, is calculated by the following formula:

- If the amount of blood lost is known: atThe nutritional administration of 200 mg of iron (= 10 ml of the FerMed preparation) leads to the same increase in hemoglobin as the transfusion of 1 unit of blood (= 400 ml with hemoglobin 150 g / l).

The amount of iron that must be replenished (mg) = number of units of lost blood x 200 or required volume of FerMed preparation (ml) = number of units of lost blood x 10.

- When the level of hemoglobin decreases: Use the previous calculation 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 in norm - the patient's Hb level) (g / l),

For example: body weight 60 kg. deficit Hb = 10 g / l => the necessary amount of iron = 150 mg => the required volume of FerMed = 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 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 / 1 time per month (depending on the concentration of serum ferritin).

Hemoglobin Correction Phase

· 150 mg of iron to increase the concentration by 10 g / l.

Side effects:

At present, the following undesirable phenomena are known to have a temporary and possible causal relationship with the administration of the FerMed preparation.

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 side of the cardiovascular system: heart palpitations, tachycardia, lowering of arterial pressure, collapsoid conditions, sensation of fever, "flushes" of blood to the face, peripheral edema.

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

From the digestive system: a taste of taste, a "metallic" taste in mouth, diffuse pain in the abdomen, pain in the epigastric region, diarrhea, nausea, vomiting.

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

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

From the immune system: allergic, anaphylactoid reactions, including angioedema, edema of the larynx.

Other: asthenia, chest pain, 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 extravasal ingestion of the drug). Phlebitis, a burning sensation, a hematoma.

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

Overdose:

Symptoms: marked reduction in arterial pressure (signs of collapse occur within 30 minutes), symptoms of hemosiderosis.

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

Interaction:

Fermed should not be given concomitantly with the medicinal forms of iron for oral administration, as it helps to reduce the absorption of iron from the gastrointestinal tract.

Treatment with iron for oral administration can begin no earlier than 5 days after the last injection.

Fermed can be mixed in one syringe only with 0.9% sodium chloride solution.

No other solutions for intravenous administration and drugs 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:

Fermed should be administered only to those patients whose diagnosis of anemia is confirmed by appropriate laboratory data (for example, serum ferritin or hemoglobin and hematocrit, erythrocyte and their parameters, mean erythrocyte volume or mean hemoglobin in erythrocyte).

It should be strictly observed the rate of administration of the drug Fermed (with rapid administration of the drug, blood pressure may decrease). A higher incidence of adverse events (in particular, a marked decrease in blood pressure), which may also be severe, is associated with an increase in dose. Thus, the administration time given in the section "Methods of administration and dosage" should be followed, even if the patient does not receive the drug in the maximum tolerable single dose.

During the administration of the FerMed preparation, it is necessary to monitor the parameters of hemodynamics.

The use of iron preparations intravenously 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 patients who have low blood iron binding capacity / or serum folate deficiency have an increased risk of allergic or anaphylactoid reactions (see section "C caution ").

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

Avoid getting the drug into the circumveneous area, because getting outside the vessel leads to necrosis of the tissues and dyeing of the skin into a brown color. 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 applied lightly, without rubbing).

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

In 1 ml of the preparation FerMed contains from 260 mg 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) (1XE = 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 transferrin saturation with iron (NTG). Determination of the number of hypochromic erythrocytes and hemoglobin in reticulocytes helps to make a decision about the need to prescribe iron preparations intravenously, when there is hyperfertinemia and low NTZ. 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. Concentration of serum ferritin above 500 μg / l (with a normal C-reactive protein), which persisted 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 effect of the drug on the ability to drive a vehicle or potentially dangerous mechanisms has not been studied.

Form release / dosage:

Solution for intravenous administration, 20 mg / ml.

Packaging:

5 ml of the drug in ampoules of colorless glass of hydrolytic class I, with a notch and a technical color mark in the form of a dot on the neck of the ampoule.

5 ampoules per contour mesh package made of PVC.

On 1 contour-and-cellular packing together with the instruction on application in a cardboard pack.

Storage conditions:

In the dark place 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 expiry date printed on the package.

Shelf life after the first opening of the container:

FROM microbiological point of view, the drug should be used immediately.

Shelf life after dilution with saline solution:

The chemical and physical stability after dilution at room temperature is 12 hours. From the microbiological point of view, the drug should be applied immediately.If the product has not been used immediately after dilution, the user is responsible for the storage conditions and time, which in any case should not exceed 3 hours at room temperature in the event that the dilution was performed under controlled and guaranteed aseptic conditions.

Terms of leave from pharmacies:On prescription

Registration number:LP-001882

Date of registration:16.10.2012

Expiration Date:16.10.2017

The owner of the registration certificate:Meditsa Artznamittel Pütter GmbH & Co. KG. KGMeditsa Artznamittel Pütter GmbH & Co. KG. KG Germany

Manufacturer: & nbsp

MEDICE ARZNEIMITTEL PUTTER, GmbH & Co. KG. KG Germany

Representation: & nbspKOSMOFARM LLCKOSMOFARM LLC

Information update date: & nbsp06.01.2017

Illustrated instructions

Instructions

Fermed (FerMed)