Instruction for use: CosmoFer

Dosage form: Solution for intravenous and intramuscular injection

Active substance: Ferri (III) hydroxydum dextranum

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 and intramuscular injection 1 ml

active substance: Iron (III) hydroxide dextran 312.5 mg

(Equivalent to 50 mg of elemental iron)

Auxiliary substances: hydrochloric acid 10% or sodium hydroxide - q.s. To pH 5.5; Water for injection (under nitrogen) - up to 1 ml.

Description

Solution: dark brown.

Pharmachologic effect

Mode of action - Replenishing the deficiency of iron, stimulating hemopoiesis.

Pharmacodynamics

The preparation contains iron in the form of a stable iron (III) complex dextran hydroxide, suitable both for intravenous and for intravenous use. An important advantage of the drug is that the iron in the complex is represented in a non-ionic water-soluble form and has very low toxicity. Complex iron (III) hydroxide dextran in its chemical structure is an analogue of the physiological complex ferritin with iron (III) hydroxide. In the body, ferritin, binding iron (III) hydroxide, provides neutralization of toxic iron ions.

Pharmacokinetics

Assimilation of iron to replenish its reserves in the body and the synthesis of hemoglobin begins immediately after the introduction of the iron (III) complex, dextran hydroxide.

Iron, introduced IV the form of iron dextran, is rapidly absorbed by the phagocytic macrophage system (SPS), especially the liver, spleen and bone marrow. The SPS cells capture iron (III) hydroxide dextran and cleave iron from the dextran carbohydrate compound, making it available to the body. Elementary iron returns to the plasma, binds to transferrin and is deposited in the form of ferritin or hemosiderin - the physiological forms of iron, and entering the bone marrow, participates in the synthesis of hemoglobin.

The serum ferritin content reaches a maximum approximately on the 7th-9th day after intravenous administration and returns to baseline in about 3 weeks.

Elevated hemopoiesis can be observed during the next 6-8 weeks.

After the / m introduction of iron (III) complex, hydroxide dextran enters the bloodstream through the capillaries and lymphatic system.

About 60% of the injected drug is absorbed within 3 days and more than 90% within 3 weeks. The rest is absorbed for several months. 2/3 of iron is removed through the digestive tract with red blood cells, bile and exfoliating cells of the epithelium.

Due to the size of the complex (165,000 Da), it is practically not excreted from the body by the kidneys.

Indication of the drug CosmoFer

Iron deficiency anemia of severe degree (with intolerance to oral iron preparations and in cases of the need for rapid replacement of iron stores).

Contraindications

Increased sensitivity to preparations containing mono- or disaccharide complexes of iron and dextran;

Anemia, not associated with iron deficiency (including hemolytic, sideroblastic, lead);

Iron overload (hemochromatosis, hemosiderosis);

bronchial asthma;

Allergic skin diseases (including eczema);

Decompensated hepatic cirrhosis and hepatitis;

infectious diseases;

Acute renal insufficiency;

Rheumatoid arthritis with symptoms of active inflammation;

Pregnancy (I trimester);

Children's age (up to 14 years).

With caution: impaired renal function; Pregnancy (II-III trimesters); Lactation period.

Application of pregnancy and breastfeeding

It should not be administered during the first trimester of pregnancy, but can be used with caution in the period of II and III trimesters and during lactation.

Side effects

Approximately 5% of patients may experience adverse reactions. The most frequent are itching, shortness of breath.

In rare cases, lowering blood pressure, nausea, dyspeptic disorders, headache, joint and muscle pain, enlarged lymph nodes, increased bilirubin levels and decreased serum calcium.

Local reactions - pain and inflammation at the injection site, in addition, with iv introduction - phlebitis, thrombophlebitis.

Large doses of iron dextran (5 ml or more) give a brown color to the serum taken 4 hours after the drug is used.

Anaphylactoid reactions are possible, up to the development of anaphylactic shock with a lethal outcome.

Interaction

CosmoFer for parenteral use is not prescribed together with oral iron preparations, because The assimilation of iron taken orally will be reduced. The interval between the parenteral application of CosmoFer and the beginning of the use of oral forms of iron should be at least 5 days.

CosmoFer should be mixed only with 0.9% sodium chloride solution or 5% glucose solution. Do not mix with solutions of other drugs.

Dosing and Administration

IV (in the form of drip infusions or slow injections), IM

Use of the drug is possible only in a hospital in conditions of availability of antishock therapy.

Patients should be under close supervision of the doctor during the administration of the drug and immediately after it for 1 hour.

The drug should be discontinued immediately if any hypersensitivity reaction or intolerance is detected during administration.

Usually the recommended dose is 100-200 mg of iron (corresponding to 2-4 ml of the drug) 2-3 times a week, depending on the hemoglobin content.

However, if the clinical situation requires rapid replacement of iron, it is possible to / into the drip injection of a total dose of CosmoFer - up to 20 mg / kg.

Intravenous drip infusions

CosmoFer can be diluted only in 0.9% solution of sodium chloride or in 5% glucose solution. A dose of 100-200 mg of iron (2-4 ml of the drug) is diluted in 100 ml of the solvent.

The first 25 mg of iron should be poured evenly for 15 minutes, if during this time no negative reactions appear, you can enter the remaining dose at a rate of not more than 100 ml in 30 minutes.

Intravenous injections

CosmoFer can be administered I / O slowly (0.2 ml / min) at a dose of 100-200 mg of iron (2-4 ml), preferably diluted in 10-20 ml of 0.9% sodium chloride solution or 5% glucose solution.

The initial dose of the drug is 25 mg of iron or 0.5 ml of the solution, which is injected / in slowly for 1-2 minutes. If there are no negative reactions within 15 minutes, the remaining dose of the drug can be continued.

The total dose of the Cosmofer is determined by the table or calculated using a formula. Immediately before use, the total dose is added with the observance of aseptic rules to the required volume (usually 500 ml) of sterile sodium chloride solution or 5% glucose solution. The total amount of CosmoFer preparation (up to 20 mg / kg) is injected intravenously into the drip for 4-6 hours.

The rate of administration can be increased to 45-60 drops / min. With an increase in the rate of administration, it is necessary to observe the patient for 1 hour after the injection.

IV the drip introduction of the drug is preferable, because Reduces the risk of the incidence of arterial hypotension.

Injections through the dialyzer

CosmoFer can be used during the procedure of hemodialysis. The drug is injected directly into the venous dialyzer circuit. The procedure for administration is the same as for intravenous administration.

Intramuscular injections

The total amount of CosmoFer is determined both by the dose table and by calculations. For intravenous injections, use undiluted preparation (2 ml, maximal - 4 ml) as a series of injections: the volume of each series is usually determined by the patient's body weight. Patients who lead a moderately active lifestyle, injections are administered daily, alternately in different buttocks. Patients with an inactive lifestyle, or bedridden patients, are injected at a frequency of 1 or 2 per week.

The drug is injected deep into the muscle (to reduce the risk of subcutaneous staining.) The drug should only be injected into the muscular mass of the outer upper quadrant of the buttock, and it cannot be inserted into the arm or other area of the body.

For adults, a 20-21G needle should be used, at least 50 mm in length; For obese patients, needles 80-100 mm in length are used, and for teenagers smaller and shorter needles (23G × 32 mm) are used. The patient should lie on his side, side up for injection or stand, transferring the weight of the body to the leg, free from injection.

To avoid penetration of the drug into the subcutaneous tissue, Z-shaped technique of skin bias before injection is recommended.

CosmoFer is administered slowly and carefully. It is important to wait a few seconds before pulling out the needle so that the muscle mass "adapts" to the volume of the injected drug.

It is not recommended to rub the injection site.

Calculation of dose

A. For patients with iron deficiency anemia

The required dose should ideally correspond to the total iron deficiency, calculated by the formula:

Body weight, kg × (necessary hemoglobin, g / l - actual hemoglobin g / l) × 0.24 + amount of iron to replenish its reserves, mg.

The factor 0.24 is calculated as follows:

A) blood volume of 70 ml / kg, i.e. About 7% of body weight;

B) the iron content in hemoglobin is 0.34%.

The factor is 0.24 = 0.0034 × 0.07 × 1000 (the transition from g to mg).

Below is a table showing the number of ml of the solution for CosmoFer injection, which can be used for iron deficiency anemia of different degrees.

The results in the table are calculated based on the achieved hemoglobin level of 150 g / l and the iron reserve of 500 mg with a body weight above 35 kg.

Table

Total dose of CosmoFer in iron deficiency anemia, ml

Note: The table and the corresponding formula are only applicable for dose determination in patients with iron deficiency anemia.

The table and formula should not be used to determine the dose in those patients who require iron substitution because of blood loss. The total need for iron reflects the amount of iron needed to restore the hemoglobin concentration to normal or close to normal levels, plus an additional amount to adequately replenish the iron reserve in most people with moderate or excessive reduction in hemoglobin. It must be remembered that iron deficiency anemia will not manifest until all the iron stores have been depleted. Therapy, therefore, should be aimed not only at replenishing hemoglobin with iron, but also with iron replenishment in general.

If the total required dose exceeds the maximum allowable daily dose, the administration should be conducted in several steps. The therapeutic effect can be observed a few days after the application of CosmoFer and manifest as an increase in the number of reticulocytes. The level of serum ferritin is a good indicator of iron replenishment. In dialysis patients receiving CosmoFer, this correlation may not appear.

B. For patients with blood loss

Iron therapy in patients with blood loss should be aimed at replenishing the amount of iron equivalent to the amount of iron in lost blood. The above table and formulas are not suitable for quickly replenishing iron stores. Quantitative estimates of blood loss and hematocrit in humans during bleeding are a convenient way of calculating the required dose of iron.

The required dose of CosmoFer to compensate for iron deficiency is calculated according to the following formulas.

1. If the volume of lost blood is unknown

IV the introduction of 200 mg of iron (4 ml of CosmoFer) will lead to an increase in hemoglobin equal to the effect of 1 unit of blood (about 400 ml with a hemoglobin level of 150 g / l, which corresponds to 0.34% of 0.4 × 150, 204 mg of iron).

Iron, which must be replaced (mg) = number of blood units lost × 4.

2. If hemoglobin is lowered, you should use the previous formula, according to which the iron stock does not need to be restored.

The amount of iron (mg) that must be replaced = body weight (kg) × 0.24 × (necessary hemoglobin g / l - actual hemoglobin g / l).

For example: body weight = 60 kg, hemoglobin deficiency = 10 g / l.

The amount of iron that must be recovered = 60 × 0.24 × 10 = 143 mg (about 3 ml of CosmoFer).

Overdose

Symptoms: hemosiderosis (acute iron overload).

Treatment: the appointment of complexing drugs (chelators) that bind iron to a chelate complex.

With the constant repeated administration of iron in a large dose, its excess accumulates in the liver and causes an inflammatory process that can lead to fibrosis.

Special instruction

The use of CosmoFer, as well as other iron-carbohydrate complexes, carries the risk of anaphylactic reactions. During the administration of the drug and immediately after admission, patients should be under the supervision of a physician.

There is an increased risk for patients with allergies. Acute anaphylactic reactions are extremely rare. They appear during the first minutes of use and are usually characterized by a sudden attack of difficulty breathing and / or cardiovascular collapse.

It should be possible to carry out anti-shock therapy (0.1% epinephrine (adrenaline), antihistamines and / or corticosteroid drugs).

When the first signs of anaphylactic reactions appear, the application of CosmoFer should be stopped immediately.

The use of CosmoFer in patients with autoimmune diseases or inflammatory conditions (systemic lupus erythematosus, rheumatoid arthritis) can cause type III allergic reactions. Cases of arterial hypotension can occur if IV injection is too fast.

Delayed hypersensitivity reactions are characterized by arthralgia, anaphylactic myalgia and sometimes fever, which can last from a few hours to 4 days after drug administration. Symptoms usually occur within 2-4 days.

The diagnosis of iron deficiency should be based on appropriate laboratory tests (serum ferritin, serum iron, transferrin saturation with iron).

Before use, check the ampoules visually for sediment and damage. Use only ampoules with a homogeneous solution that does not contain sediment.

Features of the drug at the first admission or when canceled

At the first application of the drug the recommended initial dose is 25 mg of iron or 0.5 ml of solution. If no negative reactions appear within the next 60 minutes, you can enter the remaining dose.

Influence on the ability to manage vehicles, mechanisms. Does not affect the ability to manage vehicles and mechanisms.

Release Form

Solution for intravenous and intramuscular injection, 50 mg / ml. 2 ml in ampoules. 5 amp. Is placed in a contour mesh package. 1 contour mesh package is placed in a cardboard package.

Manufacturer

Pharmacosmos A / S, Denmark

Representative office in Moscow: LLC "KOSMOFARM". Russia

Conditions of supply of pharmacies

On prescription.

Storage conditions of the drug CosmoFer

In a dry place, at a temperature of no higher than 25 ° C. Do not freeze.

Keep out of the reach of children.

Shelf life of the drug CosmoFer

Solution for intravenous and intramuscular injection 50 mg / ml - 3 years.

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