Venofer

Pharmacological properties

the active component of iron sucrose consists of multinuclear centers of iron (iii) hydroxide, surrounded on the outside by many non-covalently linked sucrose molecules. the weight of the complex is the average molecular weight, which is approximately 43 kda, which is a fairly high rate and prevents its excretion by the kidneys. the multi-core center of iron has a structure similar to that of the center of ferritin, which is a physiological iron-containing protein. the complex is designed to provide a controlled way of assimilable iron for transporting iron and preserving proteins in the body (transferrin and ferritin, respectively).

Pharmacokinetics Evaluation of ferrokinetics 100 mg of iron hydroxide sucrose complex, indicated ⁵⁹Fe and ⁵²Fe was performed among 6 patients with iron deficiency, anemia, renal anemia, or functional iron deficiency. During the period from 2 to 4 weeks after administration, the maximum assimilation of red blood cells ⁵⁹Fe ranged from 59 to 97%.

Distribution. After iv administration of a single dose of Venofer containing 100 mg of iron, C_max iron was observed 10 min after administration and reached an average value of 538 mmol / L. The volume of distribution of the central chamber corresponded well with the volume of blood plasma (≈3 L).

The introduced iron was rapidly released from the blood plasma, and the final T_½ was 6 hours. The distribution volume in equilibrium concentration was 8 liters, which indicates a weak distribution of iron in biological fluids. The iron transported by transferrin was about 31 mg / day.

Metabolism. After iv administration, iron from the complex is captured predominantly by the liver, spleen and bone marrow. In the second stage, iron is used to synthesize hemoglobin, myoglobin and other iron-containing enzymes, or is stored in the liver as ferritin.

The excretion of iron by the kidneys during the first 4 hours after the injection corresponded to 5% of the total clearance. After 24 hours, the total concentration of iron in the blood plasma was reduced to the initial level (before administration), and the excretion of sucrose by the kidneys amounted to ≈75% of the administered dose.

Indications

Iron deficiency conditions:

• if necessary, quick replenishment of iron;
• patients who do not tolerate or do not follow the regular intake of oral iron preparations;
• in the presence of active inflammatory diseases of the digestive tract, when oral iron preparations are ineffective.

Application

Venofer is administered only iv. administration can be performed using slow injection, drip iv injection or direct injection into the venous section of the dialysis system. the product is not intended for i / m administration.

Before starting treatment with the first therapeutic dose of Venofer, a test dose should be given. It is necessary to have resuscitation facilities. If during the observation period, which should last at least 15 minutes, no side effects have appeared, you can enter part of the remaining dosage.

IV drip. Venofer is preferably administered by drip infusion in order to reduce the risk of developing arterial hypotension and the risk of r-ra getting into the circulatory space.

Immediately before administration, Venofer must be diluted in 0.9% sodium chloride solution in a ratio of 1:20, for example:

• 1 ml of Venofer (20 mg of iron) in a maximum of 20 ml of sterile 0.9% sodium chloride solution;
• 5 ml of Venofer (100 mg of iron) in a maximum of 100 ml of sterile 0.9% sodium chloride solution;
• 25 ml of Venofer (500 mg of iron) in a maximum of 500 ml of sterile 0.9% sodium chloride solution.

To ensure the stability of the solution, it is not allowed to breed Venofer in larger than recommended volumes of the physiological solution.

The resulting solution is recommended to be administered at a rate of:

• 100 mg of iron for at least 15 minutes;
• 200 mg of iron for at least 30 minutes;
• 300 mg of iron for at least 1.5 hours;
• 400 mg of iron for at least 2.5 hours;
• 500 mg of iron for at least 3.5 hours

The introduction of the maximum permissible single dose of 7 mg of iron per 1 kg of body weight should be carried out for at least 3.5 hours, regardless of the total dose of the drug. In the form of infusion, the maximum tolerated dose should be prescribed no more than 1 time per week.

Before starting the first drip infusion, it is necessary to conduct a test dose: 20 mg of iron for adults and children with a body weight of ≥14 kg and half a daily dose (1.5 mg of iron / kg) for children with a body weight of 14 kg, for 15 minutes. In the absence of adverse events, you can enter at the recommended speed the portion of the solution that remains.

In / in the jet introduction. Venofer can be administered iv slowly as an undiluted solution at a rate of 1 ml / min (5 ml of Venofer (100 mg of iron) is administered in 5 minutes), but the maximum volume of the solution should not exceed 10 ml of Venofer (200 mg of iron ) for 1 injection.

Before starting the introduction, it is necessary to conduct a test dose: for adults and children with a body weight of ≥14 kg - 1 ml (20 mg of iron), and for children with a body weight of 14 kg - half the daily dose (1.5 mg of iron / kg ) slowly for 1–2 min. If during the observation period, which lasts at least 15 minutes, no side effects appear, you can enter the remainder of the drug dose.

Venofer can be injected directly into the venous section of the dialysis system, strictly following the rules described for iv injection.

Dose calculation. The dose is calculated individually in accordance with the total iron deficiency in the patients body according to the formula:

Total iron deficiency (mg) = body weight (kg) × (normal Hb level (g / l) - patients Hb level (g / l)) × 0.24 + deposited iron (mg).

For patients with a body weight of 35 kg: the normal level of Hb is 130 g / l, the amount of deposited iron is 15 mg / kg of body weight. For patients with a body weight of 35 kg: the normal level of Hb is 150 g / l, the amount of deposited iron is 500 mg. Coefficient 0.24 = 0.0034 × 0.07 × 1000 (iron content in Hb = 0.34%, blood volume = 7% of body weight, coefficient 1000 = conversion of “g” to “mg”).

The total volume of Venofer to be administered (ml) = total iron deficiency (mg) / 20 mg / ml.

In the case when the full required dose exceeds the maximum permissible single dose, fractional administration of the drug is recommended.

If within 1-2 weeks after the start of treatment there is no improvement in hematological parameters, the initial diagnosis must be reviewed.

Dose calculation for replenishing iron levels after blood loss or donation

The dose of Venofer needed to compensate for iron deficiency is determined by the following formula:

• if the amount of blood lost is known: iv administration of 200 mg of iron (= 10 ml of Venofer) leads to the same increase in Hb concentration as transfusion of 1 unit of blood (= 400 ml with a Hb concentration of 150 g / l); the amount of iron to be compensated (mg) = the number of units of lost blood × 200, or the required volume of the drug Venofer (ml) = the number of units of lost blood × 10;
• with a decrease in Hb level: use the previous formula, but it should be borne in mind that it is not necessary to replenish the iron depot. The amount of iron to be compensated (mg) = body weight (kg) × 0.24 × (normal Hb level (g / l) - patients Hb level (g / l)). For example: body weight - 60 kg, deficiency of Hb = 10 g / l, therefore - the required amount of iron = 150 mg, and the required volume of the drug Venofer = 7.5 ml.

Standard dosage

Adults and elderly patients: 5-10 ml of Venofer (100-200 mg of iron) 1-3 times a week depending on the level of Hb.

Children: there is only limited data on the use of the drug in children. In case of clinical need (for quick replenishment of the body with iron), it is recommended to administer no more than 0.15 ml of Venofer (3 mg of elemental iron) per 1 kg of body weight 1-3 times a week, depending on the level of hemoglobin.

Maximum single dose

Adults and elderly patients: for injection 10 ml of Venofer (200 mg of iron) - the duration of administration is at least 10 minutes, no more than 3 times a week; for infusion - depending on the indications, a single dose can reach 500 mg of iron. The maximum tolerated single dose is 7 mg of iron per 1 kg of body weight and is administered 1 time per week, but it should not exceed 25 ml of Venofer (500 mg of iron). The time of administration of the drug and the method of dilution are given above.

Contraindications

Non-iron deficiency anemia (e.g. hemolytic anemia, megaloblastic anemia, erythropoiesis disorders, bone marrow hypoplasia); oversaturation of the body with iron (hemoside