Iron [III] hydroxide dextran - instructions for use, dose, side effects, contraindications

The preparation contains iron in the form of a stable complex of iron [III] hydroxide dextran, suitable for both intravenous and intramuscular 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 of iron [III] hydroxide dextran by its chemical structure is an analogue of the physiological complex of ferritin with iron [III] hydroxide. In the body, ferritin, binding ferric hydroxide [III], provides neutralization of toxic iron ions.

Pharmacokinetics:

The 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 administered intravenously in the form of iron dextran, quickly absorbed by the system of phagocytic macrophages, especially the liver, spleen and bone marrow.Cells of phagocytic macrophage system capture iron [III] hydroxide dextran and cleave iron from the carbohydrate compound of dextran, 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 about 7-9 days after intravenous administration and returns to baseline in about 3 weeks.

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

After intramuscular administration, the iron [III] complex hydroxide dextran enters the bloodstream through capillaries and the lymphatic system.

About 60% of the intramuscularly injected drug is absorbed within 3 days and more than 90% - within 3 weeks. The rest is absorbed for several months. 2/3 of the 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.

Indications:

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

ICD-10

IV.E50-E64.E61.1 Insufficiency of iron

III.D50-D53.D50.9 Iron deficiency anemia, unspecified

III.D50-D53.D50 Iron-deficiency anemia

Contraindications:

Anemia, not associated with iron deficiency (including hemolytic, sideroblastic, lead).
Iron overload (hemochromatosis, hemosiderosis).
Bronchial asthma, eczema or other allergic skin diseases.
Decompensated hepatic cirrhosis and hepatitis.
Infectious diseases.
Acute kidney failure.
Rheumatoid arthritis with symptoms of active inflammation.
Pregnancy I trimester.
Children and adolescence under 18 years.
Hypersensitivity to drugs containing mono- or disaccharide complexes of iron and dextran.

Carefully:

Impaired renal function.
Pregnancy (II-III trimester).
Lactation period.

Pregnancy and lactation:

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.

Dosing and Administration:

Intravenously (in the form of drip infusions or slow injections), intramuscularly.

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 at the time of injection and immediately afterwards 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, an intravenous drip injection of a total dose of the drug, up to 20 mg / kg, is possible.

Intravenous drip infusions

The drug can be diluted only in 0.9% solution of sodium chloride or in a 5% solution of glucose. 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

The drug can be administered intravenously 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 administered intravenously slowly for 1-2 minutes. If there are no negative reactions within 15 minutes, the remaining dose of the drug can be continued.

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

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

Intravenous drip introduction of the drug is preferable, since it reduces the risk of the incidence of arterial hypotension.

Injections through the dialyzer

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

Intramuscular injections

The total amount of the drug is determined by calculations. For intramuscular 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 who are inactive, 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 can not be inserted into the arm or other area of the body.

For adults, a 20-21G needle must be used, at least 50 mm in length; For obese patients, needles 80-100 mm in length are used, and for adolescents 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 the injection.

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

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

Factor 0.24 is calculated as follows: a) blood volume of 70 ml / kg, that is about 7% of body weight; b) the iron content in hemoglobin is 0.34%. Factor 0.24 = 0.0034 × 0.07 × 1000 (transition from g to mg).

The formula should not be used to determine the dose in those patients who require iron substitution because of blood loss. The total requirement 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 carried out in several steps. The therapeutic effect can be observed a few days after the application of the drug and manifest as an increase in the number of reticulocytes. The level of serum ferritin is a good indicator of iron replenishment. Patients on dialysis receiving the drug, this correlation may not manifest.

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. 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 the drug to compensate for iron deficiency is calculated according to the following formulas.

1. If the volume of lost blood is unknown

Intravenous injection of 200 mg of iron (4 ml of the drug) 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, ie 204 mg of iron ).

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

2. If the 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 should be recovered = 60 × 0.24 × 10 = 143 mg (about 3 ml of the drug).

Side effects:

Approximately 5% of patients may experience adverse reactions. The most frequent - itching, dyspnea.

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 intravenous injection - phlebitis, thrombophlebitis.

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

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

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, the excess of it accumulates in the liver and causes an inflammatory process that can lead to fibrosis.

Interaction:

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

The drug should be mixed only with 0.9% sodium chloride solution or 5% glucose solution. Do not mix with solutions of other medicinal products.

Special instructions:

The use of the drug, 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 drug should be discontinued immediately.

The use of the drug 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 intravenous injection is performed too quickly.

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.

At the first use 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.

Instructions

Iron [III] hydroxide dextran (Ferri (III) hydroxydum dextranum)