Composition, form of production and packaging
Solution for intravenous and / m introduction of dark brown color.
1 ml
iron [III] hydroxide dextran 312.5 mg
corresponds to elemental iron 50 mg
Excipients: hydrochloric acid 10%, sodium hydroxide qs to pH 5.5, water d / and (under nitrogen) to 1 ml.
2 ml - dark glass ampoules (5) - packings of cellular contour (1) - packs of cardboard.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2011.
PHARMACHOLOGIC EFFECT
The CosmoPer preparation contains iron in the form of a stable complex of iron (III) hydroxide dextran, suitable for both intravenous and / or application. 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. Iron (III) hydroxide dextran in its chemical structure is an analogue of the physiological complex of ferritin with iron (III) hydroxide. In the body, ferritin, binding Fe (III) hydroxide, provides neutralization of toxic iron ions.
PHARMACOKINETICS
Assimilation of iron to replenish its reserves in the body and synthesis of hemoglobin begins immediately after the introduction of iron (III) hydroxide of dextran.
Iron, administered intravenously in the form of dextran iron, 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 - 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 hematopoiesis can be observed for the next 6-8 weeks.
After intramuscular injection of iron (III), dextran hydroxide enters the bloodstream through the capillaries and lymphatic system.
About 60% of intramuscularly injected iron (III) dextran is absorbed for three days and more than 90% - for three weeks. The rest is absorbed for several months.
Two thirds 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 Daltons), 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 for rapid replacement of iron reserves.
DOSING MODE
CosmoPer is used in the form of intravenous drip infusions or slow intravenous or intramuscular injections. The use of CosmoPer is possible only in a hospital with the condition of availability of anti-shock therapy. Patients should be under close supervision of the doctor at the time of drug administration and immediately afterwards for 1 hour. The use of CosmoPer should be stopped immediately if any hypersensitivity reaction or intolerance is detected during administration.
Usually the recommended dose of CosmoPer is 100-200 mg of iron (corresponding to 2 to 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 of body weight of the patient.
Intravenous drip infusion:
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 speed of no more than 100 ml in 30 minutes.
CosmoPer can be diluted only in 0.9% sodium chloride solution or in 5% glucose solution. A dose of 100-200 mg of iron (2-4 ml) is diluted in 100 ml of the solution.
Intravenous injection:
CosmoPer can be administered intravenously slowly (0.2 ml / min) at a dose of 100-200 mg iron (2-4 ml), preferably diluted in 10-20 ml 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.
The total dose of CosmoFer is determined from the table or calculated using formulas. Immediately before administration, the total dose of the drug is added with aseptic compliance to the required volume (usually 500 ml) of sterile sodium chloride solution or 5% glucose solution. The total amount of CosmoPer preparation (up to 20 mg / kg of body weight) is administered intravenously by 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 administration of the drug is preferred, since it reduces the risk of the incidence of arterial hypotension.
Injections through the dialyzer:
CosmoPer 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 injection:
The total amount of CosmoFer is determined both by the dose table and by calculations. For intramuscular injections, use undiluted preparation (2.0 ml, maximal - 4.0 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 one or two per week.
CosmoPer should be injected deep into the muscle, to reduce the risk of subcutaneous staining. The drug should be injected only into the muscle mass of the upper outer square of the buttock, you can not inject CosmoFer into the arm or other external area of ​​the body.
For adults , a 20-21 G needle must be used, at least 50 mm in length; For obese patients, needles 80-100 mm long are used, and for adolescents smaller and shorter needles (23 Gx 32 mm) are used. The patient should lie on his side, with the side for injection up, or stand, transferring the body weight to the leg, free from injection.To avoid penetration of the drug into the subcutaneous tissue, Z-shaped technique of mixing the skin before injection is recommended. CosmoPer is introduced slowly and carefully. It is important to wait a few seconds before pulling out the needle so that the muscle mass adjusts to the volume of the injected drug. It is not recommended to rub the injection site.
Calculation of dose:
For patients with iron deficiency anemia :
The required dose should ideally correspond to the total iron deficiency, calculated by the formula:
Body weight in kg? (required Hb g / l - actual Hb g / l)? 0.24 + mg of iron to replenish iron stores. Factor 0.24 is obtained as follows:
a) Blood volume of 70 ml / kg of body weight = approximately 7% of body weight
b) Iron content in hemoglobin 0.34%
Factor 0.24 = 0.0034? 0.07? 1000 (the transition from r to mg).
The table below shows the number of milliliters of Kosmofer, which should be used at different degrees of iron deficiency anemia.
The results in the table below are based on the achieved hemoglobin content of 150 g / l and the iron reserve of 500 mg with a body weight above 35 kg.
The total dose of CosmoFer in milliliters for iron deficiency anemia:
Body weight (kg) Hemoglobin content
60 g / l 75 g / l 90 g / l 105 g / l 120 g / l 135 g / l
35 25 23 20 18 15 12.5
40 27 24 22 19 16 13
45 29 26 23 20 16.5 13
50 32. 28 24 21 17 13.5
55 34 30 26 22 18 14
60 36 32 27 23 18.5 14.5
65 38 33 20 24 19.5 14.5
70 40 35 30 25 20 15
75 42 37 32 26 21 15.5
80 45 39 33 27 21.5 16
85 47 41 34 28 22 16
90 49 42 36 29 23 16.5
Note: The table and the corresponding formula are applicable for dose determination only in patients with iron deficiency anemia. The table and formula should not be used for the day of dose determination in those patients who require iron replacement 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 for sufficient replenishment of iron in most people with moderate or excessive hemoglobin reduction. It must be remembered that iron-deficiency anemia will not manifest until all the iron stores have been depleted.Therapy, in this way, 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 CosmoFer and manifest as an increase in the number of reticulocytes. The level of serum ferritin is a good indicator of the replenishment of iron reserves. In patients on dialysis receiving CosmoPer, this correlation may not appear.
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 fast iron replenishment. 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 CosmoPer to compensate for iron deficiency is calculated according to the following formulas:
If the volume of lost blood is unknown:
intake of 200 mg of iron iv (4 ml CosmoPer) will lead to an increase in hemoglobin equal to the effect of 1 unit of blood (= 400 ml with 150 g / l Hb, which equals 0.34% of 0.4-150 or 204 mg of iron).
Iron, which should be mixed (mg) = the number of blood units lost? 4,
If Hb is lowered: use the previous formula, according to which the iron stock does not need to be restored.
The amount of mg of iron that should be mixed = body weight (kg)? 0.24? (the required Hb in g / l is the actual Hb g / l).
For example: body weight = 60 kg, deficiency Hb = 10 g / l.
Iron, which must be substituted = 60? 0.24? 10 = 143 mg (about 3 ml of CosmoPer).
SIDE EFFECT
Approximately 5% of patients may experience adverse reactions.
The most frequent adverse reactions are itching, dyspnea.
In rare cases, it is possible to: lower blood pressure, nausea, dyspeptic disorders, headache, joint and muscle pain, increased lymph nodes, increased bilirubin levels, and a decrease in serum calcium.
Local reactions: pain and inflammation at the injection site, in addition, with intravenous injection - phlebitis and thrombophlebitis.
Large doses of iron dextran (5 ml or more) give a brown color to the serum taken 4 hours after the drug is applied.
Anaphylactoid reactions are possible, up to the development of anaphylactic shock with a lethal outcome.
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 renal failure;
- rheumatoid arthritis with symptoms of active inflammation;
- pregnancy I trimester;
- children and adolescence under 18;
- hypersensitivity to drugs containing mono- or disaccharide complexes of iron and dextran.
With caution :
- impaired renal function;
- Pregnancy (II - III trimester) and lactation.
PREGNANCY AND LACTATION
CosmoFer should not be assigned to during the first trimester of pregnancy, but can be used with caution in the period of II and III trimesters and during lactation.
APPLICATION FOR FUNCTIONS OF THE LIVER
Contraindicated in acute renal failure. Use with caution in case of impaired renal function.
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
Contraindicated in decompensated liver cirrhosis and hepatitis.
APPLICATION FOR CHILDREN
Contraindicated for children and adolescents under 18 years.
SPECIAL INSTRUCTIONS
Precautions for use:
The application of CosmoFer, as well as the use of 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 CosmoPer in patients with autoimmune diseases or inflammatory conditions (systemic lupus erythematosus, rheumatoid arthritis) can cause type III allergic reactions. Cases of arterial hypotension may occur if intravenous injections are 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 appear within 2-4 days.
The diagnosis of iron deficiency should be based on appropriate laboratory tests (serum ferritin, serum iron, transferrin saturation with iron).
Features of the drug at the first admission or when canceled:
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.
Impact on the ability to drive vehicles and manage mechanisms
Does not affect the ability to manage vehicles and machinery.
OVERDOSE
In the case of acute iron overload, which can manifest as hemosiderosis, iron-binding preparations (chelators). With the constant repeated administration of iron in a large dose, excess iron accumulates in the liver and causes an inflammatory process that can lead to fibrosis.
DRUG INTERACTION
CosmoPer for parenteral use is not prescribed together with oral iron preparations. the absorption 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 medicinal products.
TERMS OF RELEASE FROM PHARMACY
On prescription.
TERMS AND CONDITIONS OF STORAGE
Store in a dry place at a temperature of no higher than 25 В° C, do not freeze. Keep out of the reach of children. Shelf life - 3 years.
