Венофер®

General characteristics. Structure:

Active ingredient: gland (III) hydroxide a saccharose complex of 540 mg that is equivalent to the content of iron of 20 mg;
auxiliary ingredients: sodium hydroxide, water for injections to 1 ml.

Description: Aqueous solution of brown color.

Pharmacological properties:

Pharmacodynamics. The multinuclear centers of iron (III) of hydroxide are surrounded outside with a set not covalently of the connected molecules of sucrose. The complex which molecular mass makes about 43 cd owing to what its removal through kidneys in not changed look is impossible is as a result formed. This complex is stable and in physiological conditions does not allocate iron ions. Iron in this complex is connected with the structures similar to natural ferritin.

Pharmacokinetics. After single intravenous administration of the drug Venofer® containing 100 mg of iron the maximum concentration of iron, on average 538 µмоль, is reached 10 minutes later after an injection. The volume of distribution of the central camera almost completely corresponds to the serum volume (about 3 l). Elimination half-life about 6 hours. Distribution volume in a stable state makes about 8 l that indicates low distribution of iron in fluid mediums of an organism. Thanks to low stability of iron of saccharate in comparison with transferrin, competitive exchange of iron in favor of transferrin and as a result is observed, in 24 hours about 31 mg of iron are transferred.
Release of iron kidneys after an injection makes the first 4 hours less than 5% of the general clearance. 24 hours later the level of iron of serum is returned to initial (before introduction) to value, and about 75% of sucrose are left by a vascular bed.

Indications to use:

Венофер® it is applied to treatment of iron deficiency states in the following cases:

• in need of bystry completion of iron;
• at patients who do not transfer peroral iron preparations or do not observe the treatment mode;
• in the presence of active inflammatory diseases of intestines when peroral iron preparations are inefficient.

Route of administration and doses:

Introduction: Венофер® it is entered only intravenously - slowly struyno or kapelno, and also to the venous site of dialysis system and it is not intended for intramuscular introduction. Unacceptably single-step introduction of a full therapeutic dose of drug.
Before introduction of the first therapeutic dose, it is necessary to appoint a test dose. If during the period of observation there were intolerance phenomena, administration of drug should be stopped immediately. Before opening of an ampoule it is necessary to examine on existence of a possible deposit and damages. It is possible to use only brown solution without deposit.
Drop introduction: Венофер® it is more preferable to enter during drop infusion to reduce risk of the expressed decrease in the ABP and danger of hit of solution in perivenous space.
Just before infusion of Venofer® it is necessary to part 0,9% with chloride sodium solution in the ratio 1:20 [for example, 1 ml (20 mg of iron) in 20 ml of 0,9% of solution of sodium of chloride]. The received solution is entered with the following speed of 100 mg of iron - not less, than in 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. Introduction of the most tolerable single dose making 7 mg of iron/kg of body weight should be made within at least 3,5 hours, irrespective of the general dose of drug. Before the first drop introduction of a therapeutic dose of the drug Venofer® it is necessary to enter a test dose: 20 mg of iron to adults and children with body weight more than 14 kg and a half of a day dose (1,5 mg of iron/kg) to the children having body weight less than 14 kg within 15 minutes. In the absence of the undesirable phenomena, the rest of solution should be entered with the recommended speed.
Jet introduction: the drug Venofer® can also be administered in the form of not divorced solution intravenously slowly, with a speed (norm) of 1 ml of the drug Venofer® (20 mg of iron) one minute (5 ml of the drug Venofer® (100 mg of iron) are entered a minimum in 5 minutes). The maximum volume of drug should not exceed 10 ml of the drug Venofer® (200 mg of iron) for one injection. Before the first jet introduction of a therapeutic dose of the drug Venofer®, it is necessary to appoint a test dose: 1 ml of the drug Venofer® (20 mg of iron) to adults and children with body weight more than 14 kg, and a half of a day dose (1,5 mg of iron/kg) to the children having body weight less than 14 kg within 1-2 minutes. In the absence of the undesirable phenomena within the next 15 minutes of observation, the rest of solution should be entered with the recommended speed. After an injection, the patient is recommended to record for some time a hand in the extended situation.
Introduction to dialysis system: Венофер® it is possible to enter directly into the venous site of dialysis system, strictly following the rules described for an intravenous injection.
Calculation of a dose: The dose is calculated individually according to the general deficit of iron in an organism on a formula:
The general deficit of iron (mg) = the body weight (kg) × (the normal Hb level - the patient's Hb) (g/l) × 0,24 * + the deposited iron (mg). For patients with body weight less than 35 kg: the normal Hb level = 130 g/l, amount of the deposited iron = 15 mg/kg of body weight. For patients with body weight more than 35 kg: the normal Hb level = 150 g/l, amount of the deposited iron = 500 mg. Coefficient 0,24 = 0,0034 × 0,07 × 1000 (Content of iron in Hb = 0,34%; Blood Volume = 7% of body weight; coefficient of 1000 = transfer of "" in "mg").

Total amount of the drug Venofer®,      General deficit of iron (mg)
which needs to be entered (into ml) =              20 mg/ml

                         Cumulative therapeutic dose of the drug Venofer® for introduction:
Body weight [kg]     of Hb of 60 g/l               of Hb of 75 g/l              of Hb of 90 g/l              of Hb of 105 g/l   
                         mg of Fe     of ml           of mg of Fe      of ml           of mg of Fe   of ml           of mg of Fe      of 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

In case the general therapeutic dose exceeds the maximum admissible single dose, fractional administration of drug is recommended.
If 1-2 weeks later after an initiation of treatment improvement of hematologic indicators does not happen the drug Venofer®, it is necessary to revise the initial diagnosis.

Calculation of a dose for completion of level of iron after blood loss or delivery of autologous blood:
The drug Venofer® dose necessary for compensation of deficit of iron is counted on the following formula:

• If the amount of the lost blood is known:
intravenous administration of 200 mg of iron (= 10 ml of the drug Venofer®) leads to the same increase in concentration of Hb, as well as transfusion of 1 unit of blood (= 400 ml with concentration of Hb of 150 g/l).
Amount of iron which needs to be filled (mg) =
quantity of units of the lost blood × 200
or
The necessary volume of the drug Venofer® (ml) = quantity of units of the lost blood × 10

• At decrease in the Hb level: use the previous formula provided that the depot of iron is not required to be filled up
Amount of iron which needs to be filled with [mg] = the body weight [kg] × 0,24 × (the normal Hb level - the Hb level of the patient) (g/l),
For example: body weight is 60 kg, deficit of Hb = 10 g/l => necessary amount of iron ≡ 150 mg => the necessary volume of the drug Venofer® = 7,5 ml

Standard dosage:
Adult and elderly patients: 5-10 ml of Venofer® (100-200 mg of iron) 1-3 times a week depending on hemoglobin level. Children: There are only limited data on use of drug for children up to 3 years. The recommended dose for children of other age groups - no more than 0,15 ml of the drug Venofer® (3 mg of iron) on body weight kg 1-3 times a week depending on hemoglobin level.
The most tolerable single dose:
Adult and elderly patients: For jet introduction: 10 ml of the drug Venofer® (200 mg of iron), duration of introduction are not less than 10 minutes.
For drop introduction depending on indications the single dose can reach 500 mg of iron. The most admissible single dose makes 7 mg of iron on kg of body weight and is entered once a week, but it should not exceed 500 mg of iron. You watch time of administration of drug and a way of cultivation in the section "Routes of Administration and Doses".

Features of use:

Венофер® it has to be appointed only that patient at whom the diagnosis of anemia is confirmed with the corresponding datas of laboratory (for example, results of definition of ferritin of serum or level of hemoglobin and a hematocrit, quantity of erythrocytes and their parameters - the average volume of an erythrocyte, average content of hemoglobin in an erythrocyte or average concentration of hemoglobin in an erythrocyte). Intravenous iron preparations can cause allergic or anaphylactoid reactions which can be potentially life-threatening.
It is necessary to observe strictly drug Venofer® rate of administering (at bystry administration of drug the ABP can decrease). Higher frequency of development of undesirable by-effects (in particular - decrease in the ABP) which can also be and heavy, is associated with increase in a dose. Thus, time of administration of drug given in the section "Routes of Administration and Doses" has to be observed strictly even if the patient does not receive drug in the most tolerable single dose. The researches conducted at the patients having hypersensitivity reactions to an iron dextran showed lack of complications against the background of treatment by the drug Venofer®. It is necessary to avoid penetration of drug into perivenous space since Venofer's hit out of limits of a vessel leads to a necrosis of fabrics and brown coloring of skin. In case of development of the given complication for acceleration of removal of iron and prevention of its further penetration into surrounding fabrics, drawing to the place of an injection heparin - the containing drugs is recommended (gel or ointment are applied the easy movements, without rubbing).

Period of storage after the first opening of a container: From the microbiological point of view, drug should be used immediately.

Period of storage after cultivation by normal saline solution: Chemical and physical stability after cultivation at the room temperature makes 12 hours. From the microbiological point of view, drug should be used immediately. If drug was not used at once after cultivation, the user bears responsibility for conditions and storage time which anyway should not exceed 3 hours at the room temperature if cultivation was executed in the controlled and guaranteed aseptic conditions.

Influence on ability to driving of the car and work with mechanisms
It is improbable that the drug Venofer® can have undesirable effect on ability to driving of the car and work with mechanisms.

Side effects:

Now it is known of the following undesirable phenomena having temporary and possible causal relation with administration of the drug Venofer®. All symptoms were observed very seldom (emergence frequency less than 0,01% and more or equally to 0,001%) from a nervous system - dizziness, a headache, a loss of consciousness, paresthesias from cardiovascular system - heartbeat, tachycardia, a lowering of arterial pressure, kollaptoidny states, feeling of heat, "inflows" of blood to the person, peripheral hypostases.
From a respiratory organs. Bronchospasm, asthma.
From digestive tract - diffuse abdominal pains, pain in epigastric area, diarrhea, a food faddism, nausea, vomiting.
From integuments - an erythema, an itch, rash, pigmentation disturbance, increase in perspiration.
From a musculoskeletal system - an arthralgia, a dorsodynia, hypostasis of joints, a mialgiya, extremity pain.
From immune system - allergic, anaphylactoid reactions, including a face edema, throat hypostasis.
Disturbances of the general character and reaction in the place of an injection - an adynamy, a stethalgia, feeling of weight in breasts, weakness, pain and hypostasis in an injection site (especially at ekstravazalny hit of drug), feeling of an indisposition, pallor, temperature increase, a fever.

Interaction with other medicines:

Венофер® it should not be appointed along with dosage forms of iron for intake as promotes reduction of absorption of iron from digestive tract. Treatment by peroral iron preparations can be begun not earlier than in 5 days after the last injection
Венофер® it is possible to mix in one syringe only with sterile normal saline solution. No other solutions for intravenous administration and therapeutic drugs are allowed to be added as there is a risk of precipitation and/or other pharmaceutical interaction. Compatibility with containers from other materials, than glass, polyethylene and polyvinylchloride is not studied.

Contraindications:

Use of the drug Venofer® is contraindicated if:

• anemia is not connected with deficit of iron;
• there are overload signs iron (a hemosiderosis, hemochromatosis) or disturbance of process of its utilization;
• there is a hypersensitivity to the drug Venofer® or its components;
• I trimester of pregnancy.

With care: Patients with bronchial asthma, eczema, a polyvalent allergy, allergic reactions to other parenteral iron preparations and the persons having low iron-binding ability of serum and/or deficit of Venofer® folic acid need to appoint with care. Also care is required at introduction of iron preparations to patients with a liver failure, with acute or chronic infectious diseases and to persons at whom blood serum ferritin indicators are raised because parenterally entered iron can have adverse effect in the presence of a bacterial or viral infection.

Use during pregnancy and a lactation: Limited experience of use of the drug Venofer® for pregnant patients showed lack of undesirable influence of saccharate of iron on the course of pregnancy and health of the fruit/newborn. So far well controlled researches at pregnant women were not conducted. Results of researches of a reproduction at animals did not reveal straight lines or the mediated harmful effects on development of an embryo/fruit, childbirth or post-natal development. Nevertheless ratio assessment risk / advantage is required.
Intake of nemetabolizirovanny saccharate of iron in breast milk is improbable. Thus, Venofer® does not constitute danger to the babies who are on breastfeeding.

Overdose:

The overdose can cause an acute overload iron which is shown by hemosiderosis symptoms. At overdose it is recommended to use symptomatic means and if it is necessary, the substances connecting iron (chelates), for example Deferoxaminum in / century.

Storage conditions:

List B. To store in original packaging at a temperature from +4 °до +25 °C. Drug is not subject to freezing. To store in the places unavailable to children. Period of validity: 3 years. Not to apply after the period of validity specified on packaging.

Issue conditions:

According to the recipe

Packaging:

Solution for intravenous administration of 20 mg/ml on 5 ml or 2 ml of drug in the colourless, transparent glass ampoules (type I on the European Pharmacopoeia) having a notch on a neck of an ampoule and technical color marks in the form of a rim and a point.
On 5 ampoules in a blister strip packaging from polyvinylchloride which together with the application instruction is packed into a cardboard pack.