Instruction for use: Monofer

Dosage form: Solution for intravenous administration

Active substance: Ferri (III) hydroxydum olygoisomaltosatum

ATX

B03AC06 Iron [III] hydroxide and dextran complex

Pharmacological groups

Iron preparation [Macro and trace elements]

Iron preparation [Stimulators of hemopoiesis]

The nosological classification (ICD-10)

D50.9 Iron deficiency anemia, unspecified: Iron deficiency anemia; Lack of iron in food; Insufficient absorption of iron from the gastrointestinal tract; Insufficient food intake of iron; Hypochromic iron deficiency anemia; Hypochromic anemia; Iron deficiency anemia in pregnant women; Iron deficiency; Disturbance of absorption of iron from the digestive tract; Combined iron-folic-B12-deficient anemia; Anemia due to violations of hemoglobin synthesis and iron metabolism; Anemia in disorders of iron utilization and reutilization; Impaired iron absorption; Impaired absorption of iron; Insufficient absorption of iron in the digestive tract

E61.1 Insufficiency of iron: Insufficient food intake of iron; Iron deficiency; Iron deficiency in women during pregnancy; Deficiency of iron and folic acid in pregnancy; Iron deficiency after surgery; Latent iron deficiency; Lack of iron during pregnancy and lactation; Inadequate intake of iron from food; Increased need for iron; Increased need for iron during menstruation; Disturbances of iron absorption from the digestive tract; Severe iron deficiency

Composition

Solution for intravenous administration 1 ml

active substance: Iron (III) hydroxide oligo isomaltosate 417 mg

(Equivalent to 100 mg of iron)

Manufactured on the production site of Solufarm Pharmacities Erzoignesse GmbH, Germany

Auxiliary substances: hydrochloric acid 25% or sodium hydroxide solution 10M - to pH 5.5; Water for injection - up to 1 ml

Manufactured at the Wasserburger Arsenaimittelwerk GmbH, Germany

Auxiliary substances: 1M solution of hydrochloric acid or 1M sodium hydroxide solution to pH 5.5; Water for injection - up to 1 ml

Description

Solution: dark brown.

Pharmachologic effect

Mode of action - Replenishing the deficiency of iron.

Pharmacodynamics

The drug Monofer, the active substance of which is iron (III) hydroxide oligo isomaltosate, is a complex. Iron in the center of the complex is surrounded by an amorphous shell of molecules of an oligo-isomaltozate with a molecular mass of 1000 Da. This oligoisomaltose complex of iron (III) hydroxide is similar in structure to ferritin, which protects the body from the toxic effect of unbound iron (III) inorganic nature, because Provides a controlled and slow release of bioavailable iron with little risk of free iron formation. In view of the low toxicity of the preparation, Monofer can be used in high doses.

The effectiveness of the drug is noted in a few days after the start of treatment and is confirmed by an increase in the number of reticulocytes in the blood.

Tmax in plasma is 7-9 days after a single IV injection, and then Cmax slowly returns to the initial concentration after 3 weeks.

Pharmacokinetics

After a single intravenous injection of the iron (III) monofert drug, the oligoisomaltosate hydroxide is rapidly captured by the cells of the reticuloendothelial system (RES), mainly the liver and spleen, which then gradually release iron into the blood. T1 / 2 is 5 hours for iron in the systemic circulation and 20 hours for the combined and systemic blood flow of iron.

From the vascular bed, iron is utilized by RES cells, which split the oligoisomaltose complex of iron (III) hydroxide into iron and oligo isomaltosate. Iron immediately binds to endogenous proteins that transfer (transferrin) and retain iron (ferritin and hemosiderin). Thus, the metabolism of iron in the body is controlled physiologically, and as a result, the concentration of hemoglobin (Hb) in the blood plasma increases and the iron stores are replenished in the depot.

The monoferon in unchanged form is not excreted by the kidneys because of the large size of the complex. Small amounts of iron are excreted by the kidneys and intestines. Oligo isomaltozate is also metabolized and excreted.

Indication of the drug Monofer

Treatment of absolute or functional iron deficiency states in the following cases:

Lack of effectiveness of oral iron preparations;

The need for rapid iron replenishment.

Contraindications

Increased sensitivity to the active substance and excipients included in the preparation;

Anemia not associated with iron deficiency (eg, hemolytic);

Presence of signs of iron overload (hemochromatosis, hemosiderosis) or disruption of iron utilization;

Hepatitis and cirrhosis of the liver in the stage of decompensation;

Rheumatoid arthritis with symptoms of inflammatory process activity;

Bacteremia;

Children under 18 years of age (due to insufficient data on effectiveness and safety).

With caution: iron preparations that are injected parenterally can cause hypersensitivity reactions, including anaphylactic shock; In connection with a high risk of allergic reactions in patients with bronchial asthma, eczema, polyvalent allergy, allergic reactions to other parenteral iron preparations, as well as in patients with immune system disorders, such as systemic lupus erythematosus, rheumatoid arthritis, acute or chronic infectious diseases; At a high rate of drug administration episodes of a sudden significant decrease in blood pressure are possible.

Application of pregnancy and breastfeeding

According to preclinical studies, the isomaltose complex does not have allergenic activity and does not interact with dextran, which suggests low immunogenic potential of the Monofer preparation. In studies on animals, a teratogenic and embryotoxic effect was noted with the use of an iron preparation in single doses higher than 125 mg / kg. The maximum recommended dose for clinical use is 20 mg / kg.

Controlled clinical studies on the use of the drug Monofer in pregnant women have not been conducted, the application is recommended only in clinically justified cases. It is necessary to carefully evaluate the benefit / risk ratio for the decision on the use of Monofer during pregnancy. If the intended benefit to the mother exceeds the possible risk to the fetus, treatment can be carried out only in the second and third trimesters of pregnancy. Application in the I trimester of pregnancy is not recommended.

Isolation of the drug Monofer with breast milk is not established; The drug can be used during lactation.

Side effects

Information on the adverse effects of the drug Monofer is limited.

It is assumed that side effects are observed in more than 1% of patients.

Parenteral administration of iron-containing drugs may be accompanied by hypersensitivity reactions. In the course of clinical studies of the Monofer drug, allergic reactions were not noted.

The incidence of side effects observed during the study was evaluated as follows: very often - ≥1 / 10; Often - ≥1 / 100, <1/10; Infrequently - ≥1 / 1000, <1/100; Rarely - ≥1 / 10000, <1/1000; Very rarely - <1/10000; Frequency is unknown (cannot be estimated).

From the CVS: rarely - heart rhythm disturbances, tachycardia, lowering blood pressure; Very rarely - increased blood pressure, bradycardia in the fetus, a feeling of palpitations.

From the blood and lymphatic system: very rarely - hemolysis.

From the nervous system: infrequent - numbness, dysphonia; Rarely - loss of consciousness, convulsions, dizziness, agitation, tremor, fatigue, decreased mental ability; Very rarely - headache, paresthesia.

From the side of the organ of vision: infrequently - a violation of the clarity of visual perception.

From the side of the hearing organ: very rarely - a short-term hearing loss.

On the part of the respiratory system: infrequently - shortness of breath; Rarely - pain in the chest.

From the gastrointestinal tract: infrequently - nausea, vomiting, abdominal pain, constipation; Often - diarrhea.

On the part of the skin: infrequent - hot flashes, itching, rash; Rarely - swelling, increased sweating.

From the side of the musculoskeletal system: infrequently - muscle cramps; Rarely - myalgia, arthralgia.

From the immune system: infrequently - anaphylactoid reactions; Very rarely anaphylactic shock.

General disorders and reactions at the injection site: infrequent - a feeling of heat, chills, a feeling of malaise, skin flushing, pain and swelling at the injection site, thrombophlebitis.

Interaction

Monofer should not be administered concomitantly with medicinal forms of iron for oral administration, because Their combined use helps to reduce the absorption of iron from the digestive tract. Treatment with oral iron preparations can begin no earlier than 5 days after the last injection.

Dosing and Administration

IV, by stream or in the form of infusion of the full dose of the drug, or drop, as well as jet through the dialysis system.

The use of the drug Monofer is possible only in a hospital provided that the provision of anti-shock therapy is available. Patients should be under close supervision of medical personnel during the administration of the drug and immediately after it for 1 hour.

Determination of total iron deficiency and the required dose

Substitution therapy in patients with chronic iron deficiency anemia dose of the drug Monofer and the scheme of its use are selected for each patient individually, taking into account the definition of total iron deficiency. The optimal target hemoglobin concentration may differ in different patient groups. Follow the recommendations below. The dose of Monofer is expressed in mg of elemental iron.

Total iron deficiency, mg = body weight, kg1 × (normal concentration of Hb - patient's Hb concentration) 2, g / l × 0.243 + deposited iron, mg4.

1 It is recommended to use the ideal body weight of the patient or body weight before pregnancy.

2 In order to convert Hb, mmol, to Hb, g / l, multiply the value of Hb, mmol, by 1.61145.

3 Coefficient 2,4 = 0,0034 × 0,07 × 1000, where 0,0034 - iron content in Hb (0,34%); 0,07 - blood volume of 70 ml / kg (about 7% of body weight); 1000 - conversion factor (1 g / l = 1000 mg / l).

4 For patients with a body weight above 35 kg, the iron depot is about 500 mg.

Therapy with iron should be supplemented with both the iron content in hemoglobin and its stores in the depot. After the total iron deficiency is adjusted, patients may need to continue therapy with the Monofer drug to maintain the required hemoglobin concentration in the blood plasma, as well as other indicators indicative of iron content.

Filling of the iron in case of blood loss

Replenishment of iron deficiency after blood loss with an iron preparation should be equivalent to loss of iron.

If the concentration of Hb is reduced: the previous formula should be used, considering that there is no need to restore the iron depot:

Total iron dose, mg = body weight, kg × (normal concentration of Hb - current concentration of Hb), g / l × 2.4.

If the amount of blood loss is unknown: the use of 200 mg of iron raises hemoglobin is equivalent to 1 unit of blood.

The dose of iron for recovery, mg = number of blood loss units × 200.

Children

Not recommended for use in children - insufficient data on efficacy and safety.

Adults, including elderly patients

Monofer should not be used concomitantly with other iron preparations. Absorption of iron can be reduced.

IV by stream injection

Monofer can be administered in a dose of 100-200 mg of iron up to 3 times a week at a rate of up to 50 mg / min. The drug is diluted in 10-20 ml sterile 0.9% sodium chloride solution.

Full dose infusion

It is possible to inject completely the entire dose of Monofer as a single infusion.

In the form of a single intravenous drip infusion, Monofer can be used in a dose of up to 20 mg iron / kg. The duration of administration of the dose of the drug to 10 mg of iron / kg is more than 30 minutes. Doses of 11-20 mg of iron / kg should be administered more than 60 minutes.

If the total dose exceeds 20 mg of iron / kg, it should be divided into 2 injections with an interval between administrations of at least 1 week. The monofer is diluted in 100-500 ml of sterile 0.9% sodium chloride solution.

IV injection

The monofer should be used at doses of 200-1000 mg of iron once a week until the whole required total dose of iron is introduced.

The drug in a dose of up to 5 mg of iron / kg is administered for at least 15 minutes; 6-10 mg of iron / kg - not less than 30 minutes; 11-20 mg of iron / kg - not less than 60 minutes.

The monofer is diluted in 100-500 ml of sterile 0.9% sodium chloride solution for injection.

Introduction through the dialysis system

The monoferr can be injected directly into the venous site of the dialysis system, strictly observing the technique of IV injection.

Overdose

The drug Monofer has low toxicity, good tolerability; The risk of overdose is minimal. Overdose can develop in connection with the cumulation of iron or acute iron overload and manifests itself as symptoms of hemosiderosis. Control of the iron content in the body is carried out by determining the concentration of ferritin.

Treatment: symptomatic and, if necessary, the use of substances that bind iron (chelates).

Special instruction

Monofer should be administered only to those patients who are diagnosed with iron deficiency anemia with appropriate laboratory data (for example, serum ferritin or hemoglobin and hematocrit concentrations, erythrocyte count and parameters, mean erythrocyte volume, mean hemoglobin in erythrocyte, or mean hemoglobin concentration in erythrocyte ).

The preparation Monofer can be mixed in one syringe only with sterile saline. 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, PE and PVC, has not been studied.

IV iron preparations can cause allergic or anaphylactoid reactions, which can be potentially life-threatening.

It is necessary to strictly comply with the speed of administration of the drug Monofer (with rapid administration of the drug, blood pressure can decrease).

A higher incidence of undesirable side effects (in particular, lowering blood pressure), which may also be severe, is associated with an increase in dose. Thus, the time of administration of the drug given in the section "Method of administration and dose" should be strictly observed, even if the patient does not receive the drug in the maximum tolerable single dose.

Avoid penetration of the drug into the circumvallic space, because Getting the drug outside the vessel leads to tissue necrosis and brown staining of the skin. If this complication develops, to accelerate the excretion of iron and prevent its further penetration into surrounding tissues, it is recommended to apply the heparin-containing preparations to the injection site (gel or ointment is applied lightly without rubbing).

After diluting the drug in a sterile solution, sodium chloride of 0.9% for injection can be stored at room temperature for a maximum of 24 hours.

Influence on the ability to drive vehicles and work with machinery. Studies to study the effect of the preparation Monofer on the ability to drive vehicles and mechanisms were not conducted. Against the background of treatment with the drug Monofer it is possible to violate the clarity of visual perception and the development of episodes of increased fatigue, which can have an adverse effect if the patient's work is associated with potentially hazardous activities. In case of occurrence of the specified symptomatology it is necessary to refrain from performance of dangerous kinds of works.

Release Form

Solution for intravenous administration, 100 mg / ml. In ampoules of transparent colorless hydrolytic glass of type I (Ph. Eur.) With a white breaking point, 1, 2, 5 or 10 ml of the preparation made on the production site of Solufarm Pharmacities Ercoignesse GmbH, Germany.

In bottles of transparent colorless hydrolytic glass of type I (Ph. Eur.), Sealed with gray chlorobutyl rubber stoppers and rolled up with aluminum caps equipped with detachable polypropylene disks (FLIP OFF), 1, 2, 5 or 10 ml of the preparation made on the Wasserburger production site Arsenaimittelwerk GmbH, Germany.

2 amp. Or f. (5 or 10 ml each) or 5 amp. Or f. (1, 2, 5 or 10 ml), or 10 amp. Or f. (1 or 2 ml) in a pack of cardboard.

Manufacturer

1. Solufarm Pharmacities Erzoognisse GmbH. Germany, Industrialstrasse 3, 34212 Melsungen.

2. Wasserburger Artzaimittelwerk GmbH. Germany, Herderstraße 2 and Tegernau 18, 83512 Wasserburg.

Issued quality control: Pharmacosmos A / C. Denmark, Rervangsvey 30, DK-4300 Holbeck.

To obtain additional information about the preparation, as well as to send your complaints and information about undesirable phenomena, you can go to the following address in Russia: "Cosmopharm" LLC. 119435, Russian Federation, Moscow

Conditions of supply of pharmacies

On prescription.

Storage conditions of the drug Monofer

At a temperature not higher than 25 ° C.

Keep out of the reach of children.

Shelf life of the drug Monofer

3 years.

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